Linkage of high-density lipoprotein-cholesterol concentrations to a locus on chromosome 9p in Mexican Americans

High-density lipoproteins (HDLs) are anti-atherogenic lipoproteins that have a major role in transporting cholesterol from peripheral tissues to the liver, where it is removed(1,2). Epidemiologic studies have shown that low levels of high-density lipoprotein-cholesterol (HDL-C) are associated with an increased incidence of coronary heart disease and an increased mortality rate(3,4), indicating a protective role of high concentrations of HDL-C against atherogenesis and the development of coronary heart disease. HDL-C level is influenced by several genetic and nongenetic factors(3,5). Nongenetic factors include smoking, which has been shown to decrease the HDL-C level. Exercise and alcohol have been shown to increase HDL-C levels(6,7). Decreased HDL-C is often associated with other coronary heart disease risk factors such as obesity, hyperinsulinemia and insulin resistance, hyper-triglyceridemia and hypertension(3). Although several genes have been identified for rare forms of dyslipidemia, the genes accounting for major variation in HDL-C levels have yet to be identified(8). Using a multipoint variance components linkage approach, we found strong evidence of linkage (lod score=3.4; P=0.00004) of a quantitative trait locus (QTL) for HDL-C level to a genetic location between markers D9S925 and D9S741 on chromosome 9p in Mexican Americans. A replication study in an independent set of Mexican American families confirmed the existence of a QTL on chromosome 9p.