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

Abstract

The human TRPM8 gene encodes a receptor mediating cold sensitivity, and this 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 the Kyrgyz population. The SNPs are located in the coding regions of the gene, and three of them are confined to a 20-bp segment in exon 7. The frequencies of minor SNP alleles are as follows: rs13004520 G/C = 0.06; rs28901637 A/T = 0.13; rs11562975 G/C = 0.27; rs7593557 G/A = 0.21; rs11563071 C/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 the highlanders (living above 3200 m ASL and higher) is lower by a factor of 1.5 than in the residents of lower regions (760–3000 m ASL; p < 0.01). This result indicates a selective role of rs11562975 in adapting to cold. A comparison of haplotype frequencies in the Kyrgyz population with Europeans, East Asians, and Africans shows a clear narrowing of genotype variation in Europeans in comparison to all the others. Probably, this phenomenon is related to a decline in the population size (bottleneck effect) during evolution. We consider the exon–intron structure of the TRPM8 gene. The 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 structural–functional characterization of genes for the TRP protein family is provided.