The variability of PNPLA3 gene as a potential marker of cold adaptation in Yakuts

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. It has been reported that specific variants of patatin-like phospholipase domain-containing 3 (PNPLA3) gene, notably SNPs rs738409 and rs2294918 are associated with high risks of liver disease. PNPLA3 rs738409 polymorphism is the main determinant of fatty liver and affects development and progression of NAFLD. rs2294918 is another SNP localised in PNPLA3 gene, it is associated with reduced expression of the PNPLA3 protein, lowering the effect of the rs738409:G variant on predisposition to steatosis and liver damage. The frequencies of alleles, genotypes, haplotypes and diplotypes (combinations of genotypes at two loci) of polymorphic variants of the PNPLA3 gene (rs2294918 and rs738409) were studied in the cohort of Yakuts (n = 150) living in the Republic of Sakha (Yakutia). Genotyping of PNPLA3 (rs738409 and rs2294918) was performed by PCR-PDRF method. The single nucleotide polymorphism rs738409 (I148M) of the PNPLA3 gene in the Yakut population is characterised by a high frequency of the risk allele G (72%). Analysis of the distribution frequency of the rs2294918 polymorphism genotypes showed that the allele G was predominant in 89.3% of individuals of the studied group of Yakuts. In this study, we identified two major diplotypes [GG][GG] and [CG][GG]. The high frequency of the mutant rs738409: G variant in Yakuts may be an adaptation of the organism to low temperatures. The study of the adiponutringene may be an important key to understanding the mechanisms of adaptation to low temperatures and metabolic processes in the indigenous population of the North.