Polymorphism of 2′-5′-oligoadenylate synthetase (OAS) genes associated with predisposition to severe forms of tick-borne encephalitis in human populations of North Eurasia

摘要

2′-5′-oligoadenylate synthetases are a family of interferon-induced enzymes playing an important role in antiviral defense in mammals. In the human genome, three genes encoding functional synthetases ( , and ) form a cluster. Previously, we found that particular genotypes and/or alleles of five single nucleotide polymorphisms (SNPs) of and are associated with predisposition to severe forms of tick-borne encephalitis (TBE) in Russians. In the current study, we investigated the distribution of three of the above SNPs, rs2285932 (C/T, Ile438Ile), rs2072136 (G/A, Ser567Ser), and rs15895 (G/A, Trp720Ter relative to p71 isoform), in seven populations of North Eurasia: Caucasians (Russians, Germans from Altai region), Central Asian Mongoloids (Altaians, Khakass, Tuvinians, and Shorians), and Arctic Mongoloids (Chukchi). Interpopulational differences in genotype, allele and haplotype frequencies and in linkage disequilibrium structure for these SNPs were detected. These frequencies correlated with the ethnicity of the populations and with their supposed differential exposure to the TBE virus. In particular, the lowest frequencies of G/G genotype for SNP rs2072136 (which, according to our earlier results, is associated with predisposition to severe forms of TBE) were found in Altaians, Khakass, Tuvinians, and Shorians, who commonly contact with the TBE virus in their habitation regions. Thus, the data obtained suggest that the TBE virus might act as a selection factor for particular variants in Central Asian Mongoloids.