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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 ( OAS1 , OAS2 and OAS3 ) form a cluster. Previously, we found that particular genotypes and/or alleles of five single nucleotide polymorphisms (SNPs) of OAS2 and OAS3 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, OAS3 rs2285932 (C/T, Ile438Ile), OAS3 rs2072136 (G/A, Ser567Ser), and OAS2 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 OAS3 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 OAS variants in Central Asian Mongoloids.

molecular biology

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