Variation in the ADIPOQ gene promoter is associated with carotid intima media thickness independent of plasma adiponectin levels in healthy subjects.

AIMS: The ADIPOQ gene encodes the protein adiponectin, and decreased circulating adiponectin levels have been observed in cardiovascular disease. We investigated the role of the ADIPOQ gene single-nucleotide polymorphisms (SNPs) A-11426G, G-11391A, C-11377G, and T45G with plasma adiponectin levels and common carotid artery intima media thickness (IMT) in a cohort of healthy subjects participating in the RISC (Relationship between Insulin Sensitivity and Cardiovascular disease) study. METHODS AND RESULTS: Anthropometric and metabolic assessment and B-mode ultrasound of the carotid IMT were measured in 1306 subjects [589 men; 717 women, mean +/- SD age 43.8 +/- 8.3 years, BMI 25.5 +/- 4.0 kg/m(2)] recruited from 19 centres in 14 European countries. Carriers of the -11426G allele and homozygous carriers of the -11391G allele had significantly lower plasma adiponectin levels. These relationships remained significant after adjusting for age, sex, recruitment centre, and BMI. Carriers of SNP -11377G allele had significantly greater IMT values compared with C allele homozygotes [geometric mean (interquartile range) 601 (543-665) vs. 590 (537-647) mum, P = 0.021]. This relationship became stronger after correcting for key covariates, including plasma adiponectin levels (P = 0.011). CONCLUSION: Variation within the ADIPOQ gene promoter is directly associated with carotid IMT in healthy subjects and is independent of circulating adiponectin levels.