Polymorphism in the TRP8 gene in Kyrgyz population: putative association with highland adaptation

The human TRPM8 gene encodes a receptor mediating cold sensitivity, and this fact points to its putative role in cold adaptation. The structural variability of the TRPM8 gene for five single-nucleotide polymorphisms (SNPs) has been studied in Kyrgyz population. The SNPs are located in coding regions of the gene, and three of them are confined to a segment of 20 bp in exon 7. The frequencies of minor SNP alleles are: rs13004520 G/C = 0.06; rs28901637 А/Т = 0.13; rs11562975 G/C = 0.27; rs7593557 G/A = 0.21; rs11563071 С/G = 0.12. The analyzed sample of Kyrgyz population includes 275 individuals living at different altitudes and under drastically different climatic conditions. The frequency of the minor rs11562975 allele in highlanders (living above 2 800 m A. S. L.) is one-third lower than in residents of lower regions (760–2 800 m A. S. L.; p < 0.01). This result presumes a selective role of rs11562975 in cold adaptation. Comparison of haplotype frequencies in Kyrgyz people with Europeans, East Asians, and Africans shows a clear narrowing of genotype variation in Europeans in comparison to all others. Probably, this phenomenon is related to a population size decline (bottleneck effect) during the evolution. We consider the exon– intron structure of the TRPM8 gene. Epigenetic markers in the vicinity of the gene have been analyzed. Two strong binding sites for insulator ctcf proteins are present there. They are likely to be associated with chromatin conformation and alternative splicing regulation. A structure–functional characterization of genes for the TRP protein family is provided