In Silico and In Vitro Analyses of PNPLA۳ rs۷۳۸۴۰۹ C > G Polymorphism in Patients With Non-alcoholic Fatty Liver Disease

Background: The polymorphism associated with liver fat content, which is well-known as PNPLA۳ rs۷۳۸۴۰۹ (Patatin-like phospholipase domain-containing protein ۳), is one of the critical subjects widely investigated in the literature regarding the prevalence of non-alcoholic fatty liver disease (NAFLD) worldwide. The present research aimed to study the bioinformatics investigations of this polymorphism together with the in vitro analyses among patients with NAFLD.Materials and Methods: In this case-control study, after performing bioinformatics analysis, the laboratory examination was performed in several steps. Genomic DNA was extracted from the blood of ۵۳ NAFLD patients and ۱۰۷ subjects with normal liver ultrasounds. PNPLA۳ rs۷۳۸۴۰۹ was genotyped by the polymerase chain reaction-restriction fragment length polymorphism method. The laboratory test results, including fasting blood sugar, triglyceride, cholesterol, high-density lipoprotein, low-density lipoprotein, alanine aminotransferase, and aspartate aminotransferase were collected from medical records. Finally, statistical analysis was performed using SPSS software, version ۱۸.۰.Results: The frequency of the G allele was ۵۶% and ۳۶% among patients and in the control group, respectively. The frequency of genotypes was ۳۵.۸% and ۴۷.۷% (CC), ۱۷% and ۳۱.۸% (CG), ۴۷.۲% and ۲۰.۶% (GG) in patients and control groups, respectively. The adjusted odds ratios for PNPLA۳ rs۷۳۸۴۰۹ C > G were ۳.۰ (۹۵% confidence interval [CI]: ۱.۲۸-۶.۹۸, P = ۰.۰۱۱) and ۰.۶۸ (۹۵% CI: ۰.۲۵-۱.۸۳, P = ۰.۴۴) for GG and CG genotypes, respectively.Conclusion: The findings showed the association between the GG genotype and the presence of NAFLD. Furthermore, the bioinformatics findings suggested the probable risk of the disease incidence regarding the change of hydropathic characteristics resulting from the amino acid substitution.

Keywords:

Non-alcoholic fatty liver disease , PNPLA۳ , Adiponutrin , Polymorphism