Volume 26, Issue 4 (7-2022)                   IBJ 2022, 26(4): 252-268 | Back to browse issues page

PMID: 36000237


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Abstract:  
Genetic factors are involved in the development, progression, and severity of non-alcoholic fatty liver disease (NAFLD). Polymorphisms in genes regulating liver functions may increase liver susceptibility to NAFLD. Therefore, we conducted this literature study to present recent findings on NAFLD-associated polymorphisms from published articles in PubMed from 2016 to 2021. From 69 selected research articles, 20 genes and 34 SNPs were reported to be associated with NAFLD. These mutated genes affect NAFLD by promoting liver steatosis (PNPLA3, MBOAT7, TM2SF6, PTPRD, FNDC5, IL-1B, PPARGC1A, UCP2, TCF7L2, SAMM50, IL-6, AGTR1, and NNMT), inflammation (PNPLA3, TNF-α, AGTR1, IL-17A, IL-1B, PTPRD, and GATAD2A), and fibrosis (IL-1B, PNPLA3, MBOAT7, TCF7L2, GATAD2A, IL-6, NNMT, UCP, AGTR1, and TM2SF6). The identification of these genetic factors helps to better understand the pathogenesis pathways of NAFLD.
Type of Study: Review Article | Subject: Molecular Genetics & Genomics

References
1. Kudaravalli P, John S. Nonalcoholic fatty liver. In: Editorial Board, editor. StatPearls. Florida: StatPearls Publishing; 2021.
2. Benedict M, Zhang X. Non-alcoholic fatty liver disease: An expanded review. World journal of hepatology 2017; 9(16): 715-732. [DOI:10.4254/wjh.v9.i16.715]
3. Tomic D, Kemp WW, Roberts SK. Nonalcoholic fatty liver disease: current concepts, epidemiology and management strategies. European journal of gastroenterology and hepatology 2018; 30(10): 1103-1115. [DOI:10.1097/MEG.0000000000001235]
4. Mitra S, De A, Chowdhury A. Epidemiology of non-alcoholic and alcoholic fatty liver diseases. Translational gastroenterology and hepatology 2020; 5: 16. [DOI:10.21037/tgh.2019.09.08]
5. Ashtari S, Pourhoseingholi MA, Zali MR. Non-alcohol fatty liver disease in Asia: Prevention and planning. World journal of hepatology 2015; 7(13): 1788-1796. [DOI:10.4254/wjh.v7.i13.1788]
6. Severson TJ, Besur S, Bonkovsky HL. Genetic factors that affect nonalcoholic fatty liver disease: A systematic clinical review. World journal of gastroenterology 2016; 22(29): 6742-6756. [DOI:10.3748/wjg.v22.i29.6742]
7. Duvnjak M, Barsić N, Tomasić V, Lerotić I. Genetic polymorphisms in non-alcoholic fatty liver disease: clues to pathogenesis and disease progression. World journal of gastroenterology 2009; 15(48): 6023-6027. [DOI:10.3748/wjg.15.6023]
8. Trépo E, Valenti L. Update on NAFLD genetics: From new variants to the clinic. Journal of hepatology 2020; 72(6): 1196-1209. [DOI:10.1016/j.jhep.2020.02.020]
9. Enomoto H, Aizawa N, Hasegawa K, Ikeda N, Sakai Y, Yoh K, Takata R, Yuri Y, Kishino K, Shimono Y, Ishii N, Takashima T, Nishimura T, Nishikawa H, Iwata Y, Iijima H, Nishiguchi SH. Possible Relevance of PNPLA3 and TLL1 Gene Polymorphisms to the Efficacy of PEG-IFN Therapy for HBV-Infected Patients. International journal of molecular sciences 2020; 21(9): 3089. [DOI:10.3390/ijms21093089]
10. Lin YC, Chang PF, Chang MH, Ni YH. Genetic determinants of hepatic steatosis and serum cytokeratin-18 fragment levels in Taiwanese children. Liver international 2018; 38(7): 1300-1307. [DOI:10.1111/liv.13689]
11. Xia MF, Lin HD, Chen LY, Wu L, Ma H, Li Q, Aleteng Q, Hu Y, He WY, Gao J, Bian H, Li XY, Gao X. The PNPLA3 rs738409 C>G variant interacts with changes in body weight over time to aggravate liver steatosis, but reduces the risk of incident type 2 diabetes. Diabetologia 2019; 62(4): 644-654. [DOI:10.1007/s00125-018-4805-x]
12. Lang S, Martin A, Zhang X, Farowski F, Wisplinghoff H, Vehreschild MJGT, Krawczyk M, Nowag A, Kretzschmar A, Scholz C, Kasper P, Roderburg Ch, Mohr R, Lammert F, Tacke F, Schnabl B, Goeser T, Steffen H-M, Demir M. Combined analysis of gut microbiota, diet and PNPLA3 polymorphism in biopsy-proven non-alcoholic fatty liver disease. Liver international 2021; 41(7): 1576-1591. [DOI:10.1111/liv.14899]
13. Krawczyk M, Rau M, Schattenberg JM, Bantel H, Pathil A, Demir M, Kluwe J, Boettler T, Lammert F, Geier A, NAFLD Clinical Study Group. Combined effects of the PNPLA3 rs738409, TM6SF2 rs58542926, and MBOAT7 rs641738 variants on NAFLD severity: a multicenter biopsy-based study. Journal of lipid research 2017; 58(1): 247-255. [DOI:10.1194/jlr.P067454]
14. Krawczyk M, Bantel H, Rau M, Schattenberg JM, Grünhage F, Pathil A, Demir M, Kluwe J, Boettler T, Weber SN, Geier A, Lammert F, NAFLD CSG. Could inherited predisposition drive non-obese fatty liver disease? Results from German tertiary referral centers. Journal of human genetics 2018; 63(5): 621-626. [DOI:10.1038/s10038-018-0420-4]
15. Hudert CA, Selinski S, Rudolph B, Bläker H, Loddenkemper CH, Thielhorn R, Berndt N, Golka K, Cadenas C , Reinders J, Henning S, Bufler P, Jansen PLM, Holzhütter HG, Meierhofer D, Hengstler JG, Wiegand S. Genetic determinants of steatosis and fibrosis progression in paediatric non-alcoholic fatty liver disease. Liver international 2019; 39(3): 540-556. [DOI:10.1111/liv.14006]
16. Valentini D, Mosca A, Di Camillo C, Crudele A , Sartorelli MR, Scoppola V, Tarani L, Villani A, Raponi M, Novelli A, Alisi A. PNPLA3 gene polymorphism is associated with liver steatosis in children with Down syndrome. Nutrition, metabolism, and cardiovascular diseases 2020; 30(9): 1564-1572. [DOI:10.1016/j.numecd.2020.05.012]
17. Martínez LA, Larrieta E, Kershenobich D, Torre A. The Expression of PNPLA3 Polymorphism could be the Key for Severe Liver Disease in NAFLD in Hispanic Population. Annals of hepatology 2017; 16(6): 909-915. [DOI:10.5604/01.3001.0010.5282]
18. Akkiz H, Taskin E, Karaogullarindan U, Delik A, Kuran S, Kutlu O. The influence of RS738409 I148M polymorphism of patatin-like phospholipase domain containing 3 gene on the susceptibility of non-alcoholic fatty liver disease. Medicine 2021; 100(19): e25893. [DOI:10.1097/MD.0000000000025893]
19. Mosca A, De Cosmi V, Parazzini F, Raponi M, Alisi A, Agostoni C, Nobili V. The role of genetic predisposition, programing during fetal life, family conditions, and post-natal diet in the development of pediatric fatty liver disease. The Journal of pediatrics 2019; 211: 72-77.e4. [DOI:10.1016/j.jpeds.2019.04.018]
20. Akkiz H, Taskin E, Karaogullarindan U, Delik A, Kuran S, Kutlu O. The influence of RS738409 I148M polymorphism of patatin-like phospholipase domain containing 3 gene on the susceptibility of non-alcoholic fatty liver disease. Medicine 2021; 100(19): e25893. [DOI:10.1097/MD.0000000000025893]
21. Narayanasamy K, Karthick R, Panneerselvam P, Mohan N, Ramachandran A, Prakash R, Rajaram M. Association of metabolic syndrome and patatin-like phospholipase 3-rs738409 gene variant in non-alcoholic fatty liver disease among a Chennai-based south Indian population. The journal of gene medicine 2020; 22(4): e3160. [DOI:10.1002/jgm.3160]
22. Alam S, Islam MS, Islam S, Mustafa G, Saleh AA, Ahmad N. Association of single nucleotide polymorphism at PNPLA3 with fatty liver, steatohepatitis, and cirrhosis of liver. Indian journal of gastroenterology 2017; 36(5): 366-372. [DOI:10.1007/s12664-017-0784-y]
23. Zusi C, Mantovani A, Olivieri F, Morandi A, Corradi M, Giudice EMD, Dauriz M, Valenti L, Byrne CD, Targher G, Maffeis C. Contribution of a genetic risk score to clinical prediction of hepatic steatosis in obese children and adolescents. Digestive and liver disease 2019; 51(11): 1586-1592. [DOI:10.1016/j.dld.2019.05.029]
24. Di Costanzo A, Belardinilli F, Bailetti D, Sponziello M, D'Erasmo L, Polimeni L, Baratta F, Pastori D, Ceci F, Montali A, Girelli G, Masi BD, Angeloni A, Giannini G, Ben MD, Angelico F, Arca M. Evaluation of polygenic determinants of non-alcoholic fatty liver disease (NAFLD) by a candidate genes resequencing strategy. Scientific reports 2018; 8(1): 3702. [DOI:10.1038/s41598-018-21939-0]
25. Kalafati IP, Dimitriou M, Borsa D, Vlachogiannakos J, Revenas K, Kokkinos A, Ladas S D, Dedoussis G V. Fish intake interacts with TM6SF2 gene variant to affect NAFLD risk: results of a case-control study. European journal of nutrition 2019; 58(4):1463-1473. [DOI:10.1007/s00394-018-1675-4]
26. Jain V, Kumar A, Ahmad N, Jana M, Kalaivani M, Kumar B, Shastri Sh, Jain O, Kabra M. Genetic polymorphisms associated with obesity and non-alcoholic fatty liver disease in Asian Indian adolescents. Journal of pediatric endocrinology and metabolism 2019; 32(7): 749-758. [DOI:10.1515/jpem-2018-0543]
27. Chung GE, Lee Y, Yim JY, Choe EK, Kwak MS, Yang JI, Park B, Lee JE, Kim JA, Kim JS. Genetic polymorphisms of PNPLA3 and SAMM50 are associated with Nonalcoholic fatty liver disease in a Korean population. Gut and liver 2018; 12(3): 316-323. [DOI:10.5009/gnl17306]
28. Niriella MA, Pathmeswaran A, De Silva ST, Kasturiratna A, Perera R, Subasinghe CE, Kodisinghe K, Piyaratna CH, Rishikesawan V, Dassanayaka AS, Silva APD, Wickramasinghe R, Takeuchi F, Kato N, Silva HJ. Incidence and risk factors for non-alcoholic fatty liver disease: A 7-year follow-up study among urban, adult Sri Lankans. Liver international 2017; 37(11): 1715-1722. [DOI:10.1111/liv.13478]
29. Oniki K, Watanabe T, Kudo M, Izuka T, Ono T, Matsuda K, Sakamoto Y, Nagaoka K, Imafuku T, Ishima Y, Watanabe H, Maruyama T, Otake K, Ogata Y, Saruwatari J. Modeling of the weight status and risk of non-alcoholic fatty liver disease in elderly individuals: the potential impact of the disulfide bond-forming oxidoreductase A-like protein (DsbA-L) polymorphism on the weight status. CPT pharmacometrics and systems pharmacology 2018; 7(6): 384-393. [DOI:10.1002/psp4.12292]
30. Chinchilla-López P, Ramírez-Pérez O, Cruz-Ramón V, Canizales-Quinteros S, Domínguez-López A, Ponciano-Rodríguez G, Sánchez-Muñoz F, Méndez-Sánchez N. More evidence for the genetic susceptibility of mexican population to non-alcoholic fatty liver disease through PNPLA3. Annals of hepatology 2018; 17(2): 250-255. [DOI:10.5604/01.3001.0010.8644]
31. Wang S, Song J, Shang X, Chawla N, Yang Y, Meng X, Wang H, Ma J. Physical activity and sedentary behavior can modulate the effect of the PNPLA3 variant on childhood NAFLD: a case-control study in a Chinese population. BMC medical genetics 2016; 17(1): 90. [DOI:10.1186/s12881-016-0352-9]
32. Petta S, Di Marco V, Pipitone RM, Grimaudo S, Buscemi C, Craxì A, Buscemi S. Prevalence and severity of nonalcoholic fatty liver disease by transient elastography: Genetic and metabolic risk factors in a general population. Liver international 2018; 38(11): 2060-2068. [DOI:10.1111/liv.13743]
33. Uygun A, Ozturk K, Demirci H, Oztuna A, Eren F, Kozan S, Yilmaz Y, Kurt O, Turker T, Vatansever S, Alper E, Unsal B. The association of nonalcoholic fatty liver disease with genetic polymorphisms: a multicenter study. European journal of gastroenterology and hepatology 2017; 29(4): 441-447. [DOI:10.1097/MEG.0000000000000813]
34. Mazo DF, Malta FM, Stefano JT, Salles APM, Gomes-Gouvea MS, Nastri ACS, Almeida JR, Pinho JRR, Carrilho FJ, Oliveira CP. Validation of PNPLA3 polymorphisms as risk factor for NAFLD and liver fibrosis in an admixed population. Annals of hepatology 2019; 18(3): 466-471. [DOI:10.1016/j.aohep.2018.10.004]
35. Larrieta-Carrasco E, Flores YN, Macías-Kauffer LR, Ramírez-Palacios P , Quiterio M , Ramírez-Salazar EG , León-Mimila P , Rivera-Paredez B , Cabrera-Álvarez G, Canizales-Quinteros S , Zhang Z-F , López-Pérez TV ,Salmerón J, Velázquez-Cruz R. Genetic variants in COL13A1, ADIPOQ and SAMM50, in addition to the PNPLA3 gene, confer susceptibility to elevated transaminase levels in an admixed Mexican population. Experimental and molecular pathology 2018; 104(1): 50-58. [DOI:10.1016/j.yexmp.2018.01.001]
36. Kallwitz ER, Tayo BO, Kuniholm MH, Cai J, Daviglus M, Cooper RS, Cotler S. American ancestry is a risk factor for suspected nonalcoholic fatty liver disease in hispanic/latino adults. Clinical gastroenterology and hepatology 2019; 17(11): 2301-2309. [DOI:10.1016/j.cgh.2019.02.007]
37. Chen LZ, Ding HY, Liu SS, Jiang XJ, Xin YN, Xuan SY. Combining I148M and E167K variants to improve risk prediction for nonalcoholic fatty liver disease in Qingdao Han population, China. Lipids in health and disease 2019; 18(1): 45. [DOI:10.1186/s12944-019-0992-9]
38. Unalp-Arida A, Ruhl CE. Patatin-like phospholipase domain-containing protein 3 I148M and liver fat and fibrosis scores predict liver disease mortality in the U.S. population. Hepatology 2020; 71(3): 820-834. [DOI:10.1002/hep.31032]
39. Mosca A, Fintini D, Scorletti E, Cappa M, Paone L, Zicari A-M, Nobili V, Byrne CD. Relationship between non-alcoholic steatohepatitis, PNPLA3 I148M genotype and bone mineral density in adolescents. Liver international. 2018; 38(12): 2301-2308. [DOI:10.1111/liv.13955]
40. Fracanzani AL, Petta S, Lombardi R, Pisano J, Russello M, Consonni D, Marco VD, Cammà C, Mensi L, Dongiovanni P, Valenti L, Craxì A, Fargion S. Liver and cardiovascular damage in patients with lean nonalcoholic fatty liver disease, and association With visceral obesity. Clinical gastroenterology and hepatology 2017; 15(10): 1604-1611. [DOI:10.1016/j.cgh.2017.04.045]
41. Chatterjee A, Basu A, Das K, Chowdhury A, Basu P. Exome-wide scan identifies significant association of rs4788084 in IL27 promoter with increase in hepatic fat content among Indians. Gene 2021; 775: 145431. [DOI:10.1016/j.gene.2021.145431]
42. Mehta R, Jeiran K, Koenig AB, Otgonsuren M, Goodman Z. The role of mitochondrial genomics in patients with non-alcoholic steatohepatitis (NASH). BMC medical genetics 2016; 17(1): 63. [DOI:10.1186/s12881-016-0324-0]
43. Nobili V, Mantovani A, Cianfarani S, Alisi A, Mosca A, Sartorelli MR, Maffeis C, Loomba R, Byrne CD, Targher G. Prevalence of prediabetes and diabetes in children and adolescents with biopsy-proven non-alcoholic fatty liver disease. Journal of hepatology 2019; 71(4): 802-810. [DOI:10.1016/j.jhep.2019.06.023]
44. Stanislawski MA, Shaw J, Litkowski E, Lange EM, Perng W, Dabelea D, Lange LA. Genetic risk for hepatic fat among an ethnically diverse cohort of youth: the exploring perinatal outcomes among children study. The Journal of paediatrics 2020; 220: 146-153. [DOI:10.1016/j.jpeds.2020.01.031]
45. Trunečka P, Míková I, Dlouhá D, Hubáček JA, Honsová E, Kolesár L, Lánská V, Fraňková S, Šperl J, Jirsa M, Poledne R. Donor PNPLA3 rs738409 genotype is a risk factor for graft steatosis. A post-transplant biopsy-based study. Digestive and liver disease 2018; 50(5): 490-495. [DOI:10.1016/j.dld.2017.12.030]
46. Seko Y, Yamaguchi K, Mizuno N, Okuda K, Takemura M, Taketani H, Hara T, Umemura A , Nishikawa T, Moriguchi M, Yasui K, Kamaguchi M, Nishioji K, Mochizuki N, Kobayashi M, Mori K, Tanaka S, Matsuura K, Tanaka Y, Itoh Y. Combination of PNPLA3 and TLL1 polymorphism can predict advanced fibrosis in Japanese patients with nonalcoholic fatty liver disease. Journal of gastroenterology 2018; 53(3): 438-448. [DOI:10.1007/s00535-017-1372-8]
47. Bruschi FV, Tardelli M, Herac M, Claudel T, Trauner M. Metabolic regulation of hepatic PNPLA3 expression and severity of liver fibrosis in patients with NASH. Liver international 2020; 40(5): 1098-1110. [DOI:10.1111/liv.14402]
48. Machado CM, Leite NC, França PH, Cardoso CR, Salles GF, Villela-Nogueira CA. PNPLA3 gene polymorphism in Brazilian patients with type 2 diabetes: A prognostic marker beyond liver disease? Nutrition, metabolism, and cardiovascular diseases 2019; 29(9): 965-971. [DOI:10.1016/j.numecd.2019.06.002]
49. Liu W, Anstee QM, Wang X, Gawrieh S, Gamazon E R, Athinarayanan S, Liu Y-L, Darlay R, Cordell HJ, Daly AK, Day CP, Chalasani N. Transcriptional regulation of PNPLA3 and its impact on susceptibility to nonalcoholic fatty liver Disease (NAFLD) in humans. Aging 2016; 9(1): 26-40. [DOI:10.18632/aging.101067]
50. Serper M, Vujkovic M, Kaplan DE, Carr RM, Lee KM, Shao Q, Miller DR, Reaven PD, Phillips LS, O'Donnell CJ, Meigs JB, Wilson PWF, Vickers-Smith R, Kranzler HR, Justice AC, Gaziano JM, Muralidhar S, Pyarajan S, DuVall SL, Assimes TL, Lee JS, Tsao PS, Rader DJ, Damrauer SM, Lynch JM, Saleheen D, Voight BF, Chang K-M, VA Million Veteran Program. Validating a non-invasive, ALT-based non-alcoholic fatty liver phenotype in the million veteran program. PLoS One 2020; 15(8): e0237430. [DOI:10.1371/journal.pone.0237430]
51. Young KA, Palmer ND, Fingerlin TE, Langefeld CD, Norris JM, Wang N, Xiang AH, Guo X, Williams A H, Chen Y-D, Taylor KD, Rotter JI, Raffel LJ, Goodarzi MO, Watanabe RM, Wagenknecht LE. Genome-wide association study identifies loci for liver enzyme concentrations in Mexican Americans: the GUARDIAN Consortium. Obesity (silver spring) 2019; 27(8): 1331-1337. [DOI:10.1002/oby.22527]
52. Song G, Xiao C, Wang K, Wang Y, Chen J, Yu Y, Wang Z, Deng G, Sun X, Zhong L, Zhou C, Qi X, Wang S, Peng Z, Wang X. Association of patatin-like phospholipase domain-containing protein 3 gene polymorphisms with susceptibility of nonalcoholic fatty liver disease in a Han Chinese population. Medicine (baltimore) 2016; 95(33): e4569. [DOI:10.1097/MD.0000000000004569]
53. Kawaguchi T, Shima T, Mizuno M, Mitsumoto Y, Umemura A, Kanbara Y, Tanaka S, Sumida Y, Yasui K, Takahashi M, Matsuo K, Itoh Y, Tokushige K, Hashimoto E, Kiyosawa K, Kawaguchi M, Itoh H, Uto H, Komorizono Y, Shirabe K, Takami S, Takamura T, Kawanaka M, Yamada R, Matsuda F, Okanoue T. Risk estimation model for nonalcoholic fatty liver disease in the Japanese using multiple genetic markers. PLoS One 2018; 13(1): e0185490. [DOI:10.1371/journal.pone.0185490]
54. James G, Reisberg S, Lepik K, Galwey N, Avillach P, Kolberg L, Mägi R, Esko T, Alexander M, Waterworth D, Loomis AK, Vilo J. An exploratory phenome wide association study linking asthma and liver disease genetic variants to electronic health records from the Estonian Biobank. PLoS One 2019; 14(4): e0215026. [DOI:10.1371/journal.pone.0215026]
55. Boonvisut S, Yoshida K, Nakayama K, Watanabe K, Miyashita H, Iwamoto S. Identification of deleterious rare variants in MTTP, PNPLA3, and TM6SF2 in Japanese males and association studies with NAFLD. Lipids in health and disease 2017; 16(1): 183. [DOI:10.1186/s12944-017-0570-y]
56. Umano GR, Caprio S, Di Sessa A, Chalasani N, Dykas DJ, Pierpont B, Bale AE, Santoro N. The rs626283 variant in the MBOAT7 gene is associated with insulin resistance and fatty liver in Caucasian obese youth. The American journal of gastroenterology 2018; 113(3): 376-383. [DOI:10.1038/ajg.2018.1]
57. Thabet K, Chan HLY, Petta S, Mangia A, Berg T, Boonstra A, Brouwer WP, Lorena Abate M, Wong V WS, Nazmy M, Fischer J, Liddle C, George J, Eslam M. The membrane-bound O-acyltransferase domain-containing 7 variant rs641738 increases inflammation and fibrosis in chronic hepatitis B. Hepatology 2017; 65(6): 1840-1850. [DOI:10.1002/hep.29064]
58. Di Sessa A, Umano GR, Cirillo G, Prete AD, Iacomino R, Marzuillo P, Giudice EMD. The membrane-bound O-acyltransferase7 rs641738 variant in pediatric nonalcoholic fatty liver disease. Journal of pediatric gastroenterology and nutrition 2018; 67(1): 69-74. [DOI:10.1097/MPG.0000000000001979]
59. Viitasalo A, Eloranta AM, Atalay M, Romeo S, Pihlajamäki J, Lakka TA. Association of MBOAT7 gene variant with plasma ALT levels in children: the PANIC study. Pediatric research 2016; 80(5): 651-655. [DOI:10.1038/pr.2016.139]
60. Raimondo G, Saitta C, Lombardo D, Giraudi PJ, Rosso N, Ieni A, Lazzara S, Palmisano S, Bonazza D, Alibrandi A, Navarra G, Tiribelli C, Pollicino T. Occult hepatitis B virus infection predicts non-alcoholic steatohepatitis in severely obese individuals from Italy. Liver international 2020; 40(7): 1601-1609. [DOI:10.1111/liv.14473]
61. Xu M, Li Y, Zhang S, Wang X, Shen J, Zhang S. Interaction of TM6SF2 E167K and PNPLA3 I148M variants in NAFLD in northeast China. Annals of hepatology 2019; 18(3): 456-460. [DOI:10.1016/j.aohep.2018.10.005]
62. Li Y, Liu S, Gao Y, Ma H, Zhan S, Yang Y, Xin Y, Xuan S. Affiliations expand. Association of TM6SF2 rs58542926 gene polymorphism with the risk of non-alcoholic fatty liver disease and colorectal adenoma in Chinese Han population. BMC biochemistry 2019; 20(1): 3. [DOI:10.1186/s12858-019-0106-3]
63. Akbulut UE, Emeksiz HC, Citli S, Cebi AH, Korkmaz HAA, Baki G. IL-17A, MCP-1, CCR-2, and ABCA1 polymorphisms in children with non-alcoholic fatty liver disease. Jornal de pediatria 2019; 95(3): 350-357. [DOI:10.1016/j.jped.2018.03.005]
64. Kurbatova IV, Topchieva LV, Dudanova OP. Caspase 3, 6, 8, and 9 gene expression in peripheral blood leukocytes and plasma concentrations of IL-6 and TNF-α in carriers of different polymorphic marker -174G>C genotypes of IL-6 gene associated with the risk of nonalcoholic steatohepatitis. Bulletin of experimental biology and medicine 2017; 162(3): 370-374. [DOI:10.1007/s10517-017-3618-0]
65. Nelson JE, Handa P, Aouizerat B, Wilson L, Vemulakonda LA, Yeh MM, Kowdley KV, NASH Clinical Research Network. Increased parenchymal damage and steatohepatitis in Caucasian non-alcoholic fatty liver disease patients with common IL1B and IL6 polymorphisms. Alimentary pharmacology and therapeutics 2016; 44(11-12): 1253-1264. [DOI:10.1111/apt.13824]
66. Bhatt SP, Guleria R, Vikram NK, Vivekanandhan S, Singh Y, Gupta AK. Association of inflammatory genes in obstructive sleep apnea and non alcoholic fatty liver disease in Asian Indians residing in North India. PLoS One 2018; 13(7): e0199599. [DOI:10.1371/journal.pone.0199599]
67. Metwally M, Bayoumi A, Romero-Gomez M, Thabet K, John M, Adams LA, Huo X, Aller R, García-Monzón C, Arias-Loste MT, Bugianesi E, Miele L, Gallego-Durán R, Fischer J, Berg T, Liddle C, Qiao L, George J, Eslam M. A polymorphism in the Irisin-encoding gene (FNDC5) associates with hepatic steatosis by differential miRNA binding to the 3'UTR. Journal of hepatology 2019; 70(3): 494-500. [DOI:10.1016/j.jhep.2018.10.021]
68. Musso G, Saba F, Cassader M, Paschetta E, Michieli FD, Pinach S, Framarin L, Berrutti M, Leone N, Parente R, Ayoubi Khajekini MT, Zarovska A, Gambino R. Angiotensin II Type 1 Receptor rs5186 Gene Variant Predicts Incident NAFLD and Associated Hypertension: Role of Dietary Fat-Induced Pro-Inflammatory Cell Activation. The American journal of gastroenterology. 2019; 114(4): 607-619. [DOI:10.14309/ajg.0000000000000154]
69. Saremi L, Lotfıpanah S, Mohammadi M, Hosseinzadeh H, Hosseini-Khah Z, Johari B, Saltanatpour Z. Association between PPARGC1A single nucleotide polymorphisms and increased risk of nonalcoholic fatty liver disease among Iranian patients with type 2 diabetes mellitus. Turkish journal of medical sciences 2019; 49(4): 1089-1094. [DOI:10.3906/sag-1808-138]
70. Habibzadeh P, Honarvar B, Silawi M, Bahramjahan Sh, Kazemi A, Faghihi MA, Lankarani K. Association between rs2303861 polymorphism in CD82 gene and non-alcoholic fatty liver disease: a preliminary case-control study. Croatian medical journal 2019; 60(4): 361-368. [DOI:10.3325/cmj.2019.60.361]
71. Rezapour S, Khosroshahi SA, Farajnia H, Mohseni F, Khoshbaten M, Farajnia S. Association of 45-bp ins/del polymorphism of uncoupling protein 2 (UCP2) and susceptibility to nonalcoholic fatty liver and type 2 diabetes mellitus in North-west of Iran. BMC research notes 2021; 14(1): 169. [DOI:10.1186/s13104-021-05586-9]
72. Kurbatova IV, Topchieva LV, Dudanova OP. Gene TNF Polymorphism -308G>A (rs1800629) and Its Relationship with the Efficiency of Ursodeoxycholic Acid Therapy in Patients with Nonalcoholic Stetohepatitis. Bulletin of experimental biology and medicine 2017; 164(2): 181-185. [DOI:10.1007/s10517-017-3953-1]
73. Daijo K, Nakahara T, Inagaki Y, Nanba M, Nishida Y, Uchikawa S, Kodama K, Oya K, Morio K, Fujino H, Ono A, Murakami E, Yamauchi M, Kawaoka T, Miki D, Tsuge M, Hiramatsu A, Hayes CN, Imamura M, Aikata H, Ochi H, Chayama K. Risk factors for histological progression of non-alcoholic steatohepatitis analyzed from repeated biopsy cases. Journal of gastroenterology and hepatology 2020; 35(8): 1412-1419. [DOI:10.1111/jgh.14968]
74. Hasan EM, Abd Al Aziz RA, Sabry D, Darweesh SK, Badary HA, Elsharkawy A, Abouelkhair MM, Yosry A. Genetic Variants in nicotinamide-N-methyltransferase (NNMT) gene are related to the stage of non-alcoholic fatty liver disease diagnosed by controlled attenuation parameter (CAP)-fibroscan. Journal of gastrointestinal and liver diseases 2018; 27(3): 265-272. [DOI:10.15403/jgld.2014.1121.273.wsh]
75. Lutz SZ, Peter A, Machicao F, Lamprinou A, Machann J, Schick F, Königsrainer I, Königsrainer A, Fritsche A, Staiger H, Häring H-U, Stefan N, Kantartzis K. Genetic Variation in the 11β-hydroxysteroid-dehydrogenase 1 Gene Determines NAFLD and Visceral Obesity. The Journal of clinical endocrinology and metabolism 2016; 101(12): 4743-4751. [DOI:10.1210/jc.2016-2498]
76. Nakajima S, Tanaka H, Sawada K, Hayashi H, Hasebe T, Abe M, Hasebe C, Fujiya M, Okumura T. Polymorphism of receptor-type tyrosine-protein phosphatase delta gene in the development of non-alcoholic fatty liver disease. Journal of gastroenterology and hepatology 2018; 33(1): 283-290. [DOI:10.1111/jgh.13820]
77. Bhatt SP, Misra A, Pandey RM. rs7903146 (C/T) polymorphism of Transcription factor 7 like 2 (TCF7L-2) gene is independently associated with non-alcoholic fatty liver disease in Asian Indians. Diabetes and metabolic syndrome 2020; 14(3): 175-180. [DOI:10.1016/j.dsx.2020.02.011]
78. Anstee QM, Darlay R, Cockell S, Meroni M, Govaere O, Tiniakos D, D.Burt A, Bedossa P, Palmer J, LinLiu Y, P.Aithal G, Allison M, Yki-Järvinen H, Vacca M, Dufour J-F, Invernizzi P, Prati D. Genome-wide association study of non-alcoholic fatty liver and steatohepatitis in a histologically characterised cohort. Journal of hepatol 2020; 73(3): 505-515. [DOI:10.1016/j.jhep.2020.04.003]
79. Yuan L, Terrrault NA. PNPLA3 and nonalcoholic fatty liver disease: towards personalized medicine for fatty liver. Hepatobiliary surgery and nutrition 2020; 9(3): 353-356. [DOI:10.21037/hbsn.2019.10.35]
80. Xu R, Tao A, Zhang S, Deng Y, Chen G. Association between patatin-like phospholipase domain containing 3 gene (PNPLA3) polymorphisms and nonalcoholic fatty liver disease: a HuGE review and meta-analysis. Scientific reports; 5: 9284. [DOI:10.1038/srep09284]
81. Bruschi FV, Tardelli M, Claudel T, Trauner M. PNPLA3 expression and its impact on the liver: current perspectives. Hepatic medicine 2017; 9: 55-66. [DOI:10.2147/HMER.S125718]
82. Pingitore P, Romeo S. The role of PNPLA3 in health and disease. Biochimica et biophysica acta. Molecular and cell biology of lipids 2019; 1864(6): 900-906. [DOI:10.1016/j.bbalip.2018.06.018]
83. Hotta K, Yoneda M, Hyogo H, Ochi H, Mizusawa S, Ueno T, Chayama K, Nakajima A, Nakao K, Sekine A. Association of the rs738409 polymorphism in PNPLA3 with liver damage and the development of nonalcoholic fatty liver disease. BMC medical genetics 2010; 11: 172. [DOI:10.1186/1471-2350-11-172]
84. Salari N, Darvishi N, Mansouri K, Ghasemi H, Hosseinian-Far M, Darvishi F, Mohammadi M. Association between PNPLA3 rs738409 polymorphism and nonalcoholic fatty liver disease: a systematic review and meta-analysis. BMC endocrine disorders 2021; 21(1): 125. [DOI:10.1186/s12902-021-00789-4]
85. Thabet K, Asimakopoulos A, Shojaei M, Romero-Gomez M, Mangia A, Irving W, Berg T, Dore GJ, Gronbæk H, Sheridan D, Abate ML, Bugianesi E, Weltman M, Mollison L, Cheng W, Riordan S, Fischer J, Spengler U, Nattermann J, Wahid A, Rojas A, White R, Douglas MW, McLeod D, Powell E, Liddle C, Poorten DV, George G, Eslam M. MBOAT7 rs641738 increases risk of liver inflammation and transition to fibrosis in chronic hepatitis C. Nature communications 2016; 7: 12757. [DOI:10.1038/ncomms12757]
86. Tanaka Y, Shimanaka Y, Caddeo A, Kubo T, Mao Y, Kubota T, Kubota N, Yamauchi T, Margherita Mancina R, Baselli G, Luukkonen P, Pihlajamäki J, Yki-Järvinen H, Valenti L, Arai H, Romeo S, Kono N. LPIAT1/MBOAT7 depletion increases triglyceride synthesis fueled by high phosphatidylinositol turnover. Gut 2021; 70(1): 180-193. [DOI:10.1136/gutjnl-2020-320646]
87. Gluchowski NL, Gabriel KR, Chitraju C, Bronson RT, Mejhert N, Boland S, Wang K, Weng Lai Z, Farese Jr RV, Walther TC. Hepatocyte Deletion of Triglyceride-Synthesis Enzyme Acyl CoA: Diacylglycerol Acyltransferase 2 Reduces Steatosis Without Increasing Inflammation or Fibrosis in Mice. Hepatology 2019; 70(6): 1972-1985. [DOI:10.1002/hep.30765]
88. Buch S, Stickel F, Trépo E, Way M, Herrmann A, Dieter Nischalke H, Brosch M, Rosendahl J, Berg T, Ridinger M, Rietschel M, McQuillin A, Frank J, Kiefer F, Schreiber S, Lieb W, Soyka M, Semmo N, Aigner E, Datz C, Schmelz R, Brückner S, Zeissig S, Stephan A-M, Wodarz N, Devière J, Clumeck N, Sarrazin C, Lammert F, Gustot T, Deltenre P, Völzke H, Lerch MM, Mayerle J, Eyer F, Schafmayer C, Cichon S, M Nöthen M, Nothnagel M, Ellinghaus D, Huse K, Franke A, Zopf S, Hellerbrand C, Moreno C, Franchimont D, Morgan MY, Hampe J. A genome-wide association study confirms PNPLA3 and identifies TM6SF2 and MBOAT7 as risk loci for alcohol-related cirrhosis. Nature genetics 2015; 47(12): 1443-1448. [DOI:10.1038/ng.3417]
89. Liu Z, Que S, Zhou L, Zheng S, Romeo S, Mardinoglu A, Valenti L. The effect of the TM6SF2 E167K variant on liver steatosis and fibrosis in patients with chronic hepatitis C: a meta-analysis. Scientific reports 2017; 7(1): 9273. [DOI:10.1038/s41598-017-09548-9]
90. Liu S, Murakami E, Nakahara T, Ohya K, Teraoka Y, Makokha GN, Uchida T, Morio K, Fujino H, Ono A, Yamauchi M, Kawaoka T, Miki D, Tsuge M, Hiramatsu A, Abe-Chayama H, Hayes NC, Imamura M, Aikata H, Chayama K. In vitro analysis of hepatic stellate cell activation influenced by transmembrane 6 superfamily 2 polymorphism. Molecular medicine reports 2021; 23(1): 16. [DOI:10.3892/mmr.2020.11654]
91. Zhang RN, Shen F, Pan Q, Cao HX, Chen GY, Fan JG. PPARGC1A rs8192678 G>A polymorphism affects the severity of hepatic histological features and nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease. World journal of gastroenterology 2021; 27(25): 3863-3876. [DOI:10.3748/wjg.v27.i25.3863]
92. Liang H, Ward WF. PGC-1alpha: a key regulator of energy metabolism. Advances in physiology education 2006; 30(4): 145-151. [DOI:10.1152/advan.00052.2006]
93. Giles DA, Moreno-Fernandez ME, Divanovic S. IL-17 Axis Driven Inflammation in Non-Alcoholic Fatty Liver Disease Progression. Current drug targets 2015; 16(12): 1315-1323. [DOI:10.2174/1389450116666150531153627]
94. Lang X, Liu W, Hou Y, Zhao W, Yang X, Chen L, Yan Q, Cheng W. IL-17A polymorphism (rs2275913) and levels are associated with preeclampsia pathogenesis in Chinese patients. BMC medical genomics 2021; 14(1): 5. [DOI:10.1186/s12920-020-00840-8]
95. Tang Y, Bian Z, Zhao L, Liu Y, Liang S, Wang Q, Han X, Peng Y, Chen X, Shen L, Qiu D, Li Z, Ma X. Interleukin-17 exacerbates hepatic steatosis and inflammation in non-alcoholic fatty liver disease. Clinical and experimental immunology 2011; 166(2): 281-290. [DOI:10.1111/j.1365-2249.2011.04471.x]
96. Wieckowska A, Papouchado BG, Li Z, Lopez R, Zein NN, Feldstein AE. Increased hepatic and circulating interleukin-6 levels in human nonalcoholic steatohepatitis. The American journal of gastroenterology 2008; 103(6): 1372-1379. [DOI:10.1111/j.1572-0241.2007.01774.x]
97. Fang M, Huang Y, Zhang Y, Ning Z, Zhu L, Li X. Interleukin-6 -572C/G polymorphism is associated with serum interleukin-6 levels and risk of idiopathic pulmonary arterial hypertension. Journal of the American society of hypertension 2017; 11(3): 171-177. [DOI:10.1016/j.jash.2017.01.011]
98. Bittar MN, Carey JA, Barnard J, Fildes JE, Pravica V, Yonan N, Hutchinson IV. Interleukin 6 G-174C polymorphism influences outcome following coronary revascularization surgery. The heart surgery forum 2005; 8(3): E140-E145. [DOI:10.1532/HSF98.20041120]
99. Mirea AM, Tack CJ, Chavakis T, Joosten LAB, Toonen EJM. IL-1 family cytokine pathways underlying NAFLD: towards new treatment strategies. Trends in molecular medicine 2018; 24(5): 458-471. [DOI:10.1016/j.molmed.2018.03.005]
100. Kakino S, Ohki T, Nakayama H, Yuan X, Otabe S, Hashinaga T, Wada N, Kurita Y, Tanaka K, Hara K, Soejima E, Tajiri Y, Yamada K. Pivotal role of TNF-α in the development and progression of nonalcoholic fatty liver disease in a murine model. Hormone and metabolic research 2018; 50(1): 80-87. [DOI:10.1055/s-0043-118666]
101. Seo YY, Cho YK, Bae JC, Hae Seo M, Park SE, Rhee EJ, Park CY, Oh KW, Park SW, Lee WY. Tumor necrosis factor-α as a predictor for the development of nonalcoholic fatty liver disease: A 4-year follow-up study. Endocrinology and metabolism (Seoul, Korea) 2013; 28(1): 41-45. [DOI:10.3803/EnM.2013.28.1.41]
102. Cheng Y, An B, Jiang M, Xin Y, Xuan S. Association of tumor necrosis factor-alpha polymorphisms and risk of coronary artery disease in patients with non-alcoholic fatty liver disease. Hepatitis monthly 2015; 15(3): e26818. [DOI:10.5812/hepatmon.26818]
103. Potoupni V, Georgiadou M, Chatzigriva E, Polychronidou G, Markou E, Zapantis Gakis C, Filimidou I, Karagianni M, Anastasilakis D, Evripidou K, Ftergioti A,Togkaridou M, Tsaftaridis N, Apostolopoulos A, Polyzos SA. Circulating tumor necrosis factor-α levels in non-alcoholic fatty liver disease: A systematic review and a meta-analysis. Journal of gastroenterology and hepatology 2021; 10: 15631. [DOI:10.1111/jgh.15631]
104. Canivet CM, Bonnafous S, Rousseau D, Leclere PS, Lacas-Gervais S, Patouraux S, Sans A, Luci C, Bailly-Maitre B, Iannelli A, Tran A, Anty R, Gual P. Hepatic FNDC5 is a potential local protective factor against non-alcoholic fatty liver. Biochimica et biophysica acta. Molecular basis of disease 2020; 1866(5): 165705. [DOI:10.1016/j.bbadis.2020.165705]
105. Karimov DD, Erdman VV, Nasibullin TR, Tuktarova IA, Somova RSH, Timasheva YR, Mustafine OE. Alu insertion-deletion polymorphism of COL13A1 and LAMA2 genes: The analysis of association with longevity. Genetika 2016; 52(10): 1185-1193. [DOI:10.1134/S1022795416100033]
106. Sjogren MH. Transaminase levels and vigorous exercise. Gastroenterology and hepatology 2007; 3(12): 913-914.
107. Eshraghian A, Iravani S, Azimzadeh P. The association between angiotensin II type 1 receptor gene A1166C polymorphism and non-alcoholic fatty liver disease and its severity. Middle East journal of digestive diseases 2018; 10(2): 96-104. [DOI:10.15171/mejdd.2018.97]
108. de Gracia Hahn D, Duret A, Mann JP. An AGTR1 variant worsens nonalcoholic fatty liver disease and the metabolic syndrome. The American journal of gastroenterology 2019; 114(4): 556-559. [DOI:10.14309/ajg.0000000000000193]
109. Hou G, Jin Y, Liu M, Wang C, Song G. UCP2-866G/A polymorphism is associated with prediabetes and type 2 diabetes. Archives of medical research 2020; 51(6): 556-563. [DOI:10.1016/j.arcmed.2020.06.001]
110. Cortez-Pinto H, Machado MV. Uncoupling proteins and non-alcoholic fatty liver disease. Journal of hepatology 2009; 50(5): 857-860. [DOI:10.1016/j.jhep.2009.02.019]
111. Lyssenko V, Lupi R, Marchetti P, Guerra SD, Orho-Melander M, Almgren P, Sjögren M, Ling C, Eriksson KF, Lethagen A-L, Mancarella R, Berglund G, Tuomi T, Nilsson P, Prato SD, Groop L. Mechanisms by which common variants in the TCF7L2 gene increase risk of type 2 diabetes. The Journal of clinical investigation 2007; 117(8): 2155-2163. [DOI:10.1172/JCI30706]
112. Musso G, Gambino R, Pacini G, Pagano G, Durazzo M, Cassader M. Transcription factor 7-like 2 polymorphism modulates glucose and lipid homeostasis, adipokine profile, and hepatocyte apoptosis in NASH. Hepatology 2009; 49(2): 426-435. [DOI:10.1002/hep.22659]
113. Kaminska D, Kuulasmaa T, Venesmaa S, Käkelä P, Vaittinen M, Pulkkinen L, Pääkkönen M, Gylling H, Laakso M, Pihlajamäki J. Adipose tissue TCF7L2 splicing is regulated by weight loss and associates with glucose and fatty acid metabolism. Diabetes 2012; 61(11): 2807-2813. [DOI:10.2337/db12-0239]
114. Smith GI, Shankaran M, Yoshino M, Schweitzer GG, Chondronikola M, Beals JW, Okunade AL, Patterson BW, Nyangau E, Field T, Sirlin CB, Talukdar S, Hellerstein MK, Klein S. Insulin resistance drives hepatic de novo lipogenesis in nonalcoholic fatty liver disease. The Journal of clinical investigation 2020; 130(3): 1453-1460. [DOI:10.1172/JCI134165]
115. Kitamoto T, Kitamoto A, Yoneda M, Hyogo H, Ochi H, Nakamura T, Teranishi H, Mizusawa S, Ueno T, Chayama K, Nakajima A, Nakao K, Sekine A, Hotta K. Genome-wide scan revealed that polymorphisms in the PNPLA3, SAMM50, and PARVB genes are associated with development and progression of nonalcoholic fatty liver disease in Japan. Human genetics 2013; 132(7): 783-792. [DOI:10.1007/s00439-013-1294-3]
116. Chen L, Lin Z, Jiang M, Lu L, Zhang H, Xin Y, Jiang X, Xuan S. Genetic variants in the SAMM50 gene create susceptibility to nonalcoholic fatty liver disease in a Chinese Han population. Hepatitis monthly 2015; 15(10): e31076. [DOI:10.5812/hepatmon.31076]
117. Rector RS, Thyfault JP, Uptergrove GM, Morris EM, Naples SP, Borengasser SJ, Mikus CR, Laye MJ, Laughlin MH, Booth FW, Ibdah JA. Mitochondrial dysfunction precedes insulin resistance and hepatic steatosis and contributes to the natural history of non-alcoholic fatty liver disease in an obese rodent model. Journal of hepatology 2010; 52(5): 727-736. [DOI:10.1016/j.jhep.2009.11.030]
118. Sanyal AJ, Campbell-Sargent C, Mirshahi F, Rizzo WB, ContosMJ, Sterling RK, Luketic VA, Shiffman ML, Clore JN. Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology 2001; 120(5): 1183-1192. [DOI:10.1053/gast.2001.23256]
119. Matsuura K, Sawai H, Ikeo K, Ogawa S, Iio E, Isogawa M, Shimada N, Komori A, Toyoda H, Kumada T. Genome-wide association study identifies TLL1 variant associated with development of hepatocellular carcinoma after eradication of hepatitis C virus infection. Gastroenterology 2017; 152(6): 1383-1394. [DOI:10.1053/j.gastro.2017.01.041]
120. Lee UE, Friedman SL. Mechanisms of hepatic fibrogenesis. Best practice and research. Clinical gastroenterology 2011; 25(2): 195-206. [DOI:10.1016/j.bpg.2011.02.005]
121. Bayoumi A, Jalil I, Metwally M, Adams LA, Aller R, García-Monzón C, Arias-Loste MT, Miele L, Petta S, Craxì A, Gallego-Durán R. Genetic variation in the TLL1 gene is not associated with fibrosis in patients with metabolic associated fatty liver disease. PLoS One 2020; 15(12): e0243590. [DOI:10.1371/journal.pone.0243590]
122. Komatsu M, Kanda T, Urai H, Kurokochi A, Kitahama R, Shigaki S, Ono T, Yukioka H, Hasegawa K, Tokuyama H, Kawabe H, Wakino S, Itoh H. NNMT activation can contribute to the development of fatty liver disease by modulating the NAD+ metabolism. Scientific reports 2018; 8(1): 8637. [DOI:10.1038/s41598-018-26882-8]
123. Zou X, Ramachandran P, Kendall TJ, Pellicoro A, Dora E, Aucott RL, Manwani K, Yung Man T, Chapman KE. 11Beta-hydroxysteroid dehydrogenase-1 deficiency or inhibition enhances hepatic myofibroblast activation in murine liver fibrosis. Hepatology 2018; 67(6): 2167-2181. [DOI:10.1002/hep.29734]
124. Kim M, Morales LD, Jang IS, Cho YY, Kim DJ. Protein tyrosine phosphatases as potential regulators of STAT3 signaling. International journal of molecular sciences 2018; 19(9): 2708. [DOI:10.3390/ijms19092708]
125. Chakraborty D, Šumová B, Mallano T, Chen C-W, Distler A, Bergmann C, Ludolph I, Horch RE, Gelse K, Ramming A, Distler O, Schett G, Šenolt L, Distler JHW. Activation of STAT3 integrates common profibrotic pathways to promote fibroblast activation and tissue fibrosis. Nature communications 2017; 8(1): 1130. [DOI:10.1038/s41467-017-01236-6]
126. Kim MC, Lee JI, Kim JH, Kim HJ, Cho YK, Jeon WK, Kim BI, Sohn W. Serum zinc level and hepatic fibrosis in patients with nonalcoholic fatty liver disease. PLoS One 2020; 15(10): e0240195. [DOI:10.1371/journal.pone.0240195]
127. Lisboa QC, Nardelli MJ, Pereira PA, Miranda DM, s Ribeiro SN, Neves Costa RS, Azevedo Versiani C, Teixeira Vidigal PV. PNPLA3 and TM6SF2 polymorphisms in Brazilian patients with nonalcoholic fatty liver disease. World journal of hepatology 2020; 12(10): 792-806 [DOI:10.4254/wjh.v12.i10.792]
128. Tam V, Patel N, Turcotte M, Bossé Y, Paré G, Meyre D. Benefits and limitations of genome-wide association studies. Nature reviews. Genetics 2019; 20(8): 467-484. [DOI:10.1038/s41576-019-0127-1]

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