Apelin gene polymorphism influences apelin expression and obesity phenotypes in Chinese women

Abstract

Apelin, which is a newly identified adipokine, is related to obesity and insulin resistance. A positive correlation between plasma apelin concentrations and obesity traits was reported. We tested associations between apelin gene (APLN) polymorphisms, BMI, and waist circumference (WC) and compared APLN expression levels in cells of different genotypes. Four tagging single nucleotide polymorphisms (SNPs) and one promoter SNP were genotyped in 1627 Chinese subjects. Because APLN was located on the chromosome X, statistical analyses were conducted in a sex-specific manner. Adipocytes of different genotypes were derived from the omental fat tissue of 10 women. We treated the primary adipocytes with high glucose plus insulin because of a close relation between insulin resistance and obesity. SNP rs3115757 was significantly associated with BMI and WC in women. Compared with the CG or GG genotype, the CC genotype had an OR of 2.07 (95% CI: 1.23, 3.49) for having a high WC (P = 0.006) and an OR of 2.29 (95% CI: 1.25, 4.19) for having a BMI (in kg/m(2)) ≥27 (P = 0.007). None of the SNPs was associated with BMI or WC in men. In adipocytes that carried the CC genotype of rs3115757, APLN messenger RNA levels and protein concentrations were higher in cells treated with high glucose plus insulin than in those with normal glucose. There was no difference between the 2 conditions in adipocytes of the CG or GG genotype. Both association and functional studies suggested that APLN polymorphisms were associated with risks of obesity phenotypes.