Human genetics of variation in high-density lipoprotein cholesterol

Longitudinal population studies have confirmed plasma levels of high-density lipoprotein (HDL) cholesterol to be an important inverse coronary risk factor. Although environmental influences are known to regulate HDL cholesterol levels, genetic factors are also known to be important, and over 25 candidate genes have been proposed to be associated with variation in HDL cholesterol levels. A variety of monogenic conditions of extremely low or high HDL cholesterol has helped to delineate the physiology of HDL cholesterol metabolism in humans, which has led to the development of new therapeutic approaches to HDL cholesterol. However, most causes of genetic variation in HDL cholesterol in the general population are likely oligogenic or polygenic. We review the monogenic disorders associated with both high and low HDL cholesterol and the relevance of mutations and polymorphisms in these genes to variation in HDL cholesterol levels in the general population.