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Linked PNPLA3 polymorphisms confer susceptibility to nonalcoholic steatohepatitis and decreased viral load in chronic

Qin Pan1, Rui-Nan Zhang1, Yu-Qin Wang1

  • 1Qin Pan, Rui-Nan Zhang, Yu-Qin Wang, Feng Shen, Jia-Fa Lu, Chan-Yan Zhu, Shu-Yi Zhang, Yi-Ming Chen, Wan-Lu Sun, Jian-Gao Fan, Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.

World Journal of Gastroenterology
|August 1, 2015
PubMed

Insights

Certain PNPLA3 gene variations increase the risk of nonalcoholic fatty liver disease (NAFLD) in patients with chronic hepatitis B (CHB). These genetic factors also influence disease severity and hepatitis B virus (HBV) levels.

Area of Science:

  • Genetics and Hepatology
  • Molecular Biology
  • Viral Hepatitis Research

Background:

  • Chronic hepatitis B (CHB) and nonalcoholic fatty liver disease (NAFLD) are significant global liver diseases.
  • Co-occurrence of CHB and NAFLD presents complex clinical challenges and potential for accelerated liver damage.
  • Genetic factors, such as PNPLA3 polymorphisms, are implicated in NAFLD pathogenesis.

Purpose of the Study:

  • To investigate the association between specific PNPLA3 polymorphisms and the presence of NAFLD in patients with CHB.
  • To evaluate the impact of these polymorphisms on the clinical and histopathological characteristics of NAFLD in the context of CHB.
  • To determine the relationship between PNPLA3 genotypes and hepatitis B virus (HBV) DNA levels in CHB patients with or without NAFLD.

Main Methods:

  • A cohort study involving Han Chinese patients with biopsy-proven CHB, with or without NAFLD, and healthy controls.
  • Genotyping of PNPLA3 polymorphisms (rs738409, rs3747206, rs4823173, rs2072906) using gene sequencing.
  • Clinical, biochemical, metabolic, and histopathological data were analyzed, alongside serum HBV DNA levels.

Main Results:

  • Four linked PNPLA3 single nucleotide polymorphisms (SNPs) — rs738409 G, rs3747206 T, rs4823173 A, and rs2072906 G alleles — were significantly associated with increased susceptibility to NAFLD in CHB patients.
  • These PNPLA3 genotypes correlated with a higher risk of nonalcoholic steatohepatitis (NASH) and liver fibrosis in patients with concurrent CHB and NAFLD.
  • Patients with specific PNPLA3 risk genotypes exhibited significantly lower serum HBV DNA levels compared to those with non-risk genotypes.

Conclusions:

  • PNPLA3 polymorphisms are strongly linked to NAFLD susceptibility, NASH development, and liver fibrosis in individuals with CHB.
  • These genetic variations also play a role in modulating HBV viral load dynamics in CHB patients.
  • The findings highlight the importance of genetic profiling in managing patients with coexisting CHB and NAFLD.
Abstract

Keywords:
Chronic hepatitis BHepatitis B virusNonalcoholic fatty liver diseasePNPLA3Single-nucleotide polymorphism

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