Arya Rector, Duggirala Ravindranath, Almasy Laura, Rainwater David L, Mahaney Michael C, Cole Shelley, Dyer Thomas D, Williams Ken, Leach Robin J, Hixson James E, MacCluer Jean W, O'Connell Peter, Stern Michael P, Blangero John
Division of Clinical Epidemiology, Department of Medicine, University of Texas Health Science Center, San Antonio, Texas, USA.
Nat Genet. 2002 Jan;30(1):102-5. doi: 10.1038/ng810. Epub 2001 Dec 17.
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. 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, 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. 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. Decreased HDL-C is often associated with other coronary heart disease risk factors such as obesity, hyperinsulinemia and insulin resistance, hypertriglyceridemia and hypertension. 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. 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.
高密度脂蛋白（HDL）是抗动脉粥样硬化脂蛋白，在将胆固醇从外周组织转运至肝脏并在肝脏中被清除的过程中起主要作用。流行病学研究表明，高密度脂蛋白胆固醇（HDL-C）水平低与冠心病发病率增加和死亡率上升相关，这表明高浓度的HDL-C对动脉粥样硬化和冠心病的发展具有保护作用。HDL-C水平受多种遗传和非遗传因素影响。非遗传因素包括吸烟，吸烟已被证明会降低HDL-C水平。运动和饮酒已被证明会增加HDL-C水平。HDL-C降低通常与其他冠心病危险因素相关，如肥胖、高胰岛素血症和胰岛素抵抗、高甘油三酯血症和高血压。虽然已经确定了几种导致罕见形式血脂异常的基因，但导致HDL-C水平主要变异的基因尚未确定。使用多点方差成分连锁分析方法，我们发现墨西哥裔美国人中HDL-C水平的一个数量性状位点（QTL）与9号染色体9p上标记D9S925和D9S741之间的遗传位置存在强连锁证据（lod分数=3.4；P=0.00004）。在一组独立的墨西哥裔美国家庭中进行的重复研究证实了9号染色体9p上存在一个QTL。
