Adiponectin gene variants and the risk of coronary heart disease: a 16-year longitudinal study

OBJECTIVE: Circulating adiponectin levels have been shown to be associated with a risk of coronary heart disease (CHD). However, its primary role in protecting against the development of CHD remains controversial due to conflicting observations in prospective studies. To gain further insight into the primary role of adiponectin, our major objective was to investigate the relationship between single nucleotide polymorphisms (SNPs) of the adiponectin gene (ADIPOQ) and incident CHD in a population-based cohort with no CHD at baseline. DESIGN AND METHODS: We conducted a 16-year longitudinal study in 2196 subjects from the Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS). During 33 862 person-years of follow-up, 184 subjects developed CHD (cumulative incidence rate=5.4 per 1000 person-years). Nine ADIPOQ SNPs with potential functional relevance or shown to be associated with adiponectin levels and/or CHD were genotyped. RESULTS: Among the nine ADIPOQ SNPs, +276G>T (rs1501299) was independently associated with incident CHD in men but not in women, even after adjustments for traditional cardiovascular risk factors (Padjusted=5.5×10(-3) to 0.023; hazard ratio=1.39-1.54). Furthermore, there was a significant association of the T allele of +276G>T with a lower adiponectin level (P=0.027; β (95% CI)=-0.05 (-0.10, -0.01). CONCLUSIONS: This study demonstrated that +276G>T may be an independent predictor of CHD development. Our findings suggest that low adiponectin levels, as may be influenced by +276G>T, confer a higher risk of CHD, in keeping with a role of hypoadiponectinaemia in the development of CHD in the general population.