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) mm, 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.