Variability of PNPLA3 and GCKR genes and their influence on biochemical parameters in residents of the Republic of Sakha (Yakutia)

The article presents a study of the frequencies of PNPLA3 and GCKR gene variants in samples of Yakuts, Evenks, and Russians. A total of 728 people living in the Sakha Republic (Yakutia) participated (331 Yakuts, 147 Evenks, and 250 Russians). Single nucleotide polymorphisms were determined by polymerase chain reaction followed by restriction fragment length polymorphism analysis. The study revealed significant differences between the studied samples. For the rs738409 polymorphism of the PNPLA3 gene, the G allele was 72-75% in Yakuts and Evenks versus 53% in Russians. For the rs2294918 polymorphism, the protective allele A is virtually absent in Yakuts (6.7%) and very rare in Evenks (17%), the Russian population has a significantly higher proportion of A (43%). For rs1260326 of the GCKR gene, the risk allele T was more common in Russians than in Yakuts and Evenks. For the associated SNP rs780094, Russians have a higher percentage of the risk allele A, approximately 48% versus 40% in Yakuts and 44% in Evenks. Linkage disequilibrium (LD) analysis between the pair of polymorphisms rs738409 and rs2294918 in the PNPLA3 gene showed an extremely weak association between these SNPs. Polymorphisms rs780094 and rs1260326 GCKR demonstrated strong linkage in all three studied samples. In the Russian sample, an association was noted between the genotype of the rs738409 PNPLA3 polymorphism and the concentration of triglycerides, and polymorphisms of the GCKR gene showed a significant effect on ALT activity. The obtained data are consistent with the hypothesis that some pathological alleles became established in northern populations due to previous adaptive advantages, but in modern conditions, they have transformed from beneficial to harmful.

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