Association of the 276G→T polymorphism of the adiponectin gene with cardiovascular disease risk factors in nondiabetic Koreans

Background: The adiponectin gene is known to modulate adiponectin concentrations and diabetes mellitus development. Objective: We assessed whether adiponectin gene variants contribute to circulating adiponectin, insulin resistance (IR), or cardiovascular disease risk factors. Design: Nondiabetic subjects [n = 902; x̄ ± SE age: 42.5 ± 0.53 y; body mass index (BMI; in kg/m²): 24.7 ± 0.11] were genotyped for 2 single-nucleotide polymorphisms (SNPs), 45T→G and 276G→T. Results: After adjustment for age, sex, and BMI, subjects with the G allele for the SNP 276 had significantly higher concentrations of triacylglycerol and small dense LDL (sdLDL) and smaller LDL particle size than did T/T subjects. G/G subjects at SNP 276 had significantly lower plasma adiponectin and higher homeostasis model assessment (HOMA) of IR and urinary prostaglandin F2α man did T/T subjects. In the SNP 45-276 haplotype test, we also observed that subjects with the X/X haplotype had significantly higher plasma adiponectin after adjustment than did TG/TG or TG/X haplotype subjects. In the highest BMI group (BMI ≥ 26), T/T subjects had lower HOMA-IR (P = 0.011) and higher plasma adiponectin (P = 0.026) at SNP 276 than did G/G or G/T subjects. These patterns were also seen for adiponectin in haplotype groups. However, no significant genotype effect for SNP 45T→G was observed. Conclusions: The 276G→T polymorphism of the adiponectin gene modulates circulating adiponectin and IR, particularly in obese states. G allele carriers also have higher oxidative stress, higher sdLDL concentrations, and smaller LDL particle size. Therefore, the presence of the G allele in the adiponectin gene at SNP 276 could be a significant contributor to higher cardiovascular disease risk in Koreans, independent of common environmental factors.