The Evaluation of Significance of Uncoupling Protein Genes UCP1, UCP2, UCP3, UCP4, UCP5, and UCP6 in Human Adaptation to Cold Climates

Six isoforms of uncoupling proteins (UCPs) exist, spanning from UCP1 to UCP6. A precise physiological function has only been established for UCP1, which is involved in non-shivering thermogenesis, but the functions of other UCPs are still not fully defined. Therefore, the purpose of the present study is to search for indications of the involvement of nine polymorphic variants of UCP1-6 genes in human adaptation to cold climates using four criteria: (1) the presence of associations of polymorphic variants of UCP genes with levels of thyroid-stimulating hormone, free triiodothyronine, and free thyroxine; (2) the presence of associations of polymorphic variants of UCP genes with changes in thyroid homeostasis (SPINA); (3) the presence of associations of polymorphic variants of UCP genes with body surface area; (4) the presence of signals of directional selection to cold climate for polymorphic variants of UCP genes. As a result of the evaluation, the highest scores for cold adaptation traits were recorded for polymorphic variants rs3811787 of the UCP1 gene and rs1800849 of the UCP3 gene. We suggest that the results obtained indicate the importance of uncoupling proteins UCP1 and UCP3 in human adaptation to cold through processes of non-shivering and shivering thermogenesis.