Barkhash A V, Babenko V N, Kobzev V F, Romashchenko A G, Voevoda M I
Mol Biol (Mosk). 2010 Nov-Dec;44(6):985-93.
2'-5'-oligoadenylate synthetases are a family of interferon-induced enzymes which play an important role in the antiviral defense in mammals. In 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) located within OAS2 and OAS3 genes are associated with predisposition to severe forms of tick-borne encephalitis (TBE) in Russian population. In current study we investigated the distribution of three of that SNPs (OAS3rs2285932 (C/T Ile438Ile), OAS3rs2072136 (G/A, Ser567Ser) and OAS2 rs15895 (G/A, Trp720Ter relative to p71 isoform)) in seven populations from North Eurasia: Caucasians (Russians and Germans (from Altai region)), Central Asian Mongoloids (Altaians, Khakasses, Tuvinians and Shorians) and Arctic Mongoloids (Chukchi). Differences between populations in genotype, allele and haplotype frequencies and in linkage disequilibrium structure for these SNPs were detected. We found that these frequencies correlate with the ethnicity of the populations and with their supposed differential exposure to TBE virus. Particularly, the lowest frequencies of G/G genotype for OAS3 gene rs2072136 SNP (that according to our previously obtained data is associated with predisposition to severe forms of TBE) were found in Altaians, Khakasses, Tuvinians and Shorians who may highly contact with TBE virus in places of their habitation. Thus, data obtained allow to suppose that TBE virus might act as a selection factor for particular OAS genes variants in Central Asian Mongoloids.
2'-5'-寡腺苷酸合成酶是一类由干扰素诱导产生的酶，在哺乳动物的抗病毒防御中发挥重要作用。在人类基因组中，编码功能性合成酶的三个基因（OAS1、OAS2和OAS3）形成一个基因簇。此前我们发现，位于OAS2和OAS3基因内的五个单核苷酸多态性（SNP）的特定基因型和/或等位基因与俄罗斯人群中严重型蜱传脑炎（TBE）的易感性相关。在当前研究中，我们调查了这三个SNP（OAS3rs2285932（C/T，Ile438Ile）、OAS3rs2072136（G/A，Ser567Ser）和OAS2 rs15895（G/A，相对于p71亚型的Trp720Ter））在北亚七个群体中的分布情况：高加索人（俄罗斯人和德国人（来自阿尔泰地区））、中亚蒙古人种（阿尔泰人、哈卡斯人、图瓦人和绍尔人）以及北极蒙古人种（楚科奇人）。检测了这些SNP在群体间基因型、等位基因和单倍型频率以及连锁不平衡结构的差异。我们发现这些频率与群体的种族以及他们假定的对TBE病毒的不同暴露情况相关。特别是，在阿尔泰人、哈卡斯人、图瓦人和绍尔人这些在居住地区可能与TBE病毒有高度接触的人群中，发现OAS3基因rs2072136 SNP的G/G基因型频率最低（根据我们之前获得的数据，该基因型与严重型TBE的易感性相关）。因此，所获得的数据表明TBE病毒可能是中亚蒙古人种中特定OAS基因变体的选择因素。
