Effect of CETP Loss-of-Function Variant on Risk of CVD in Chinese Adults

Cholesteryl ester transfer protein (CETP) loss-of-function variant was associated with major changes in HDL metabolism, but had no significant effects on the risk of cardiovascular disease in Chinese adults, according to the results of research presented Nov. 15 during AHA 2016.

Zhengming Chen, MD, et al., genotyped rs2303790 in 91,850 individuals in China, of whom 17,850 had conventional lipid measurements and 4,650 had lipoprotein subtypes measured by Nuclear Magnetic Resonance-metabolomics. Linear and logistic regression models yielded adjusted per allele effects for continuous traits and for 11,650 occlusive cardiovascular disease events (comprising 75 percent ischemic strokes and 25 percent major coronary events).

The results of the study show that the CETP loss-of-function variant was associated with an increase of 0.53 standard deviations per allele in HDL-C (equivalent to 6.1 mg/dL), but had little effect on LDL-C. Significant effects of the CETP loss-of-function variant on circulating metabolites included larger HDL particle size, smaller LDL particle size, and within HDL particles, increased cholesterol esters and reduced triglycerides relative to total lipids.

However, according to the authors, "the CETP loss-of-function variant was not associated with lower risk of occlusive cardiovascular disease or with the individual outcomes ischemic stroke or major coronary events." They add that "these results do not support the hypothesis that increasing HDL-C by CETP inhibition confers protection against cardiovascular disease in East Asians."

Keywords: AHA16, American Heart Association, AHA Annual Scientific Sessions, Adult, Cardiovascular Diseases, Cohort Studies, Incidence, Lipid Metabolism, Morbidity, Risk


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