Association of rs4646287 Polymorphism with the Risk of Hepatitis B Virus Infection and the Progression of Hepatocellular Carcinoma in an Iranian Population

Authors
Hassan Akrami 1
Mohammad Reza Fattahi 1
Mastaneh Zeraatiannejad 2
Jamal Sarvari 3
Yousef Nikmanesh 1
Zahra Mansourabadi 1
Zahra Yazdani 4
1 Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
2 Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
3 Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
4 Department of Biology, College of Sciences, Shiraz University, Shiraz 71467-13565, Iran.
10.61882/ibj.4979
Abstract
Background: Hepatitis B virus (HBV) is responsible for more than one million deaths annually, mainly due to HBV-related diseases and hepatocellular carcinoma (HCC). HBV enters hepatocytes and interacts with the sodium taurocholate co-transporting polypeptide. While several single nucleotide polymorphisms (SNPs) have been linked to HBV infection and HCC, further research is needed to clarify the precise role of SNPs. The relationship of the rs4646287 SNP with the risk of HBV infection and the progression of cirrhosis and HCC has been investigated in different populations. This study aimed to evaluate the association of the rs4646287 SNP with HBV infection, cirrhosis, and HCC in an Iranian population.

Methods: The whole blood DNA was extracted from healthy individuals and patients with HBV, cirrhosis, and HCC. Primers for the C and T variants were designed using Primer1. The genotypes of the samples were identified using Tetra-ARMS PCR. The Tetra-ARMS PCR products were analyzed by electrophoresis on 2.5% agarose gels.

Results: Individuals with the rs4646287 TT genotype exhibited a significantly reduced risk of developing cirrhosis and HCC compared to healthy controls. The TT genotype also showed a decreased correlation between the HBV group and those with cirrhosis and HCC.

Conclusion: Our findings suggest that the rs4646287 TT genotype is associated with a lower risk of developing HBV-related diseases and HCC in an Iranian population.
Keywords
Hepatitis B virus
Hepatocellular Carcinoma
Single nucleotide polymorphisms
Iranian Biomedical Journal
Volume 29, Issue 4 - Serial Number 119
July and August 2025
Pages 260-266