Relationships between Uncoupling Protein Genes UCP1, UCP2 and UCP3 and Irisin Levels in Residents of the Coldest Region of Siberia

Abstract

Currently, it is known that irisin can participate in the processes of thermoregulation and browning of adipose tissue, and, therefore, it is possible that it is involved in the microevolutionary mechanisms of adaptation to a cold. The aim of this study is to investigate the relationship between the uncoupling protein genes (UCP1, UCP2, UCP3) and the irisin levels in the residents of the coldest region of Siberia. The sample consisted of 279 Yakut people (185 females, 94 males, average age 19.8 ± 2.03 years). The females plasma irisin concentration was 8.33 ± 2.74 mcg/mL and the males was 7.76 ± 1.86 mcg/mL. Comparative analysis of irisin levels with the genotypes of six studied SNP-markers in females revealed a significant association of irisin with rs1800849-UCP3. The TT genotype of rs1800849 was associated with elevated levels of irisin (p = 0.01). It was also found that this TT genotype in females was associated with reduced weight and height (p = 0.03). We searched for natural selection signals for the T-allele rs1800849-UCP3; as a result of which, it was found that this allele has a significantly high frequency of distribution in northern (45%, CI:0.42–0.484) compared with southern Asian populations (28%, CI:0.244–0.316) (p = 0.01). The results obtained indicate the probable involvement of irisin and the UCP3 gene in thermoregulation, and the spread of its allelic variants is probably related to adaptation to a cold climate.

Epigenetic features of far northern Yakutian population

“…A large study of Siberian populations identified candidate genes for adaptation to the cold, associated with energy and metabolic regulation, as well as contraction of vascular smooth muscle [9]. Besides, leptin and irisin, which play an important role in the processes of adaptation to the cold, become the focus of several other studies of the Yakutian cohort [13][14][15]. However, genetic studies for Siberian populations are often limited to mitochondrial DNA, Y chromosome or single-nucleotide polymorphisms [8,9,16,17], while epigenome-wide studies have not been performed.…”