Significance of the influence of patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 polymorphism on non alcoholic fatty liver disease

 Enas Mahmoud Foda1, Shereen Abu Bakr Saleh1, Moheb Shoraby Eskandaros2, Nashwa Nagy El-Khazragy3, Heba Mohamed Abu Bakr4, Yasmin Mohamed Massoud5, Ghada Abdelrahman Mohamed1 1Gastroenterology and Hepatology Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo 11591, Egypt. 2Department of General Surgery, Faculty of Medicine, Ain Shams University, Cairo 11591, Egypt. 3Departments of Clinical Pathology-Hematology and Genetics and Molecular Biology, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt. 4Department of Internal Medicine, El Sahel Teaching Hospital, Cairo 11697, Egypt. 5Department of Tropical Medicine, Faculty of Medicine, Ain Shams University, Cairo 11591, Egypt. Corresponding author: Ghada Abdelrahman Mohamed, MD, Assist. Prof of Internal Medicine, Gastroenterology and Hepatology Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo 11591, Egypt. ORCID: 0000-0003-0320-1011. Email: ghadaabdelrahman@med.asu.edu.eg. DOI:10.21608/ajgh.2024.313440.1061. Submission date:18 August 2024. Revision date: 26 September 2024. Acceptance date: 20 October 2024. First online: 26 October 2024.

Abstract 

Background: Non-alcoholic fatty liver disease (NAFLD) is characterized by diffuse hepatocyte steatosis. The pathogenesis of NAFLD is not recognized. It has become apparent that genetic, environmental, and metabolic factors drive NAFLD. Moreover, earlier studies have observed 

that some polymorphisms raise the likelihood of NAFLD. Among these, the most robustly observed was the relationship between NAFLD risk and patatin-like phospholipase domain-containing 3 (PNPLA3). Aim: We aimed to assess the effect of the rs738409 polymorphism of the PNPLA3 gene (encoding I148m) on NAFLD. Patients and Methods: This study, which included 30 participants, was conducted with meticulous attention to detail and thoroughness: 20 patients with NAFLD and 10 healthy participants as a control group. Participants were diagnosed according to a liver biopsy taken during surgery from patients who were candidates for bariatric surgery and as part of a predonation assessment for candidates for donation in liver transplantation. Genotyping of the PNPLA3 gene variant (rs738409 C/G) was assessed using the TaqMan assay quantitative polymerase chain reaction in blood cells. Results: Considering the distribution of the PNPLA3 gene variant (rs738409 C/G), a greater prevalence of heterozygous rs738409 CG and homozygous rs738409 GG variants occurred in the NAFLD patients in contrast to the control group (p = 0.048). In addition, NAFLD patients with the homozygous GG variant had a higher incidence of hepatic fibrosis (p = 0.018). Furthermore, PNPLA3 gene polymorphism significantly predicted hepatic steatosis and fibrosis in NAFLD patients (p = 0.033 and p < 0.001, respectively). Conclusion: The PNPLA3 rs738409 polymorphism is significantly associated with the susceptibility and severity of non-alcoholic fatty liver disease.