PNPLA3 rs738409 polymorphism in Patients with Type 2 Diabetes and Concomitant Liver Pathology in Yakutia

Abstract

Background: The pathogenetic mechanisms of type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) are closely related. Currently, multiple studies have demonstrated a link between the PNPLA3 148M variant and the development and progression of NAFLD, including liver fibrosis. The aim of our research was to study the distribution of alleles and genotypes of the PNPLA3 rs738409 SNP in Russians and Yakuts living in Yakutia, as well as to search for associations of the PNPLA3 rs738409 SNP in patients with T2D and non-alcoholic fatty liver disease / non-alcoholic steatohepatitis. Methods and Results: The study included 179 patients (28 Russians and 151 Yakuts) with T2D and concomitant liver diseases of non-infectious origin. The comparison group consisted of 147 healthy volunteers of Russian ethnicity and 246 healthy volunteers of Yakut ethnicity. The PNPLA3 738409 SNP was analyzed by PCR-RFLP reaction. The results found a significant difference between the frequencies of the PNPLA3 rs738409 genotypes and alleles in Russians and Yakuts, both among healthy volunteers and in T2D patients with liver diseases. The frequency of the G allele occurrence in the group of healthy Yakuts was significantly higher (OR- 3.313; 95% CI: 2.444-4.499; P<0.001) than in the group of healthy Russians. No significant differences were found for the PNPLA3 rs738409 genotype and allele frequencies among a healthy sample and a sample of T2D patients with non-alcoholic fatty liver disease / non-alcoholic steatohepatitis, both in the Russian and Yakut populations.