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 <i>UCP1</i>-<i>6</i> genes in human adaptation to cold climates using four criteria: (1) the presence of associations of polymorphic variants of <i>UCP</i> genes with levels of thyroid-stimulating hormone, free triiodothyronine, and free thyroxine; (2) the presence of associations of polymorphic variants of <i>UCP</i> genes with changes in thyroid homeostasis (SPINA); (3) the presence of associations of polymorphic variants of <i>UCP</i> genes with body surface area; (4) the presence of signals of directional selection to cold climate for polymorphic variants of <i>UCP</i> genes. As a result of the evaluation, the highest scores for cold adaptation traits were recorded for polymorphic variants rs3811787 of the <i>UCP1</i> gene and rs1800849 of the <i>UCP3</i> gene. We suggest that the results obtained indicate the importance of uncoupling proteins <i>UCP1</i> and <i>UCP3</i> in human adaptation to cold through processes of non-shivering and shivering thermogenesis.