[Association of UCP1 rs1800592, UCP2 rs660339, and UCP3 rs1800849 polymorphisms with body mass index and lipid metabolism parameters in the indigenous population of the North of Western Siberia].

Abstract

Population-based data on the association between genes regulating non-shivering thermogenesis (UCP) and adipose tissue metabolism are fragmentary and yield inconsistent results. The indigenous populations of high-latitude regions have been the least studied. This study aimed to assess the association of UCP1 (rs1800592), UCP2 (rs660339), and UCP3 (rs1800849) genotypes with body mass index (BMI) and lipid profile markers in the indigenous population of northern Western Siberia.

Material and methods: The study groups consisted of 12 males aged 27-50 and 39 females 18-64 years old belonging to the Ob Ugrians (ethnic Khanty and Mansi). Blood samples and data on BMI, blood plasma levels of total cholesterol (TC), highdensity lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) were collected. Genotyping of genomic DNA isolated from the subjects' blood samples was performed at the polymorphic UCP1 (A/G, rs1800592), UCP2 (C/T, rs660339), and UCP3 (C/T, rs1800849) loci. Data analysis was performed using the Statistica 12.0 software package (StatSoft, USA). For the maximum accuracy of the Hardy-Weinberg equilibrium compliance test in a small sample, we used the HWE exact test (Fisher's method) implemented in the Cog-Genomics/PLINK statistical package. An intergroup comparison of indicators in carriers of different genotypes was carried out using the Mann-Whitney test. When comparing biochemical parameters in groups with different genotypes, the Bonferroni correction for multiple comparisons was used.

Results: In carriers of the AA*UCP1 genotype, BMI values (27.2±5.6 kg/m2; n=30) were higher than in individuals with GG+AG genotypes (23.7±3.94 kg/m2; n=21, p=0.015). No associations were found between BMI and UCP2 and UCP3 polymorphisms. Female subjects with the homozygous TT*UCP2 genotype had increased plasma TG levels (p=0.033) and higher TG/HDL ratios compared with C*UCP2 allele carriers. Homozygotes for the C*UCP3 allele differed from carriers of the T* allele (CT and TT genotypes) in having higher LDL-C levels (p=0.036).

Conclusion: The study confirmed the association of UCP1 gene variants with BMI and of UCP2 and UCP3 genes with lipid profile parameters in the ethnic Khanty and Mansi studied group. The association of UCP1 with BMI in the subjects of this study does not agree with the conclusions found in the scientific literature about an increased risk of obesity among G* allele carriers in Caucasian samples. The associations between UCP2-3 and lipid metabolism parameters in Ob Ugrians are consistent with those reported in Mongoloid populations. The specificity of the phenotypic manifestations of UCP polymorphism in different racial groups requires further investigation.