Ko Yu-Lin, Hsu Lung-An, Hsu Kuang-Hung, Ko Yu-Hsien, Lee Ying-Shiung
The First Cardiovascular Division, Department of Internal Medicine, Chang Gung Memorial Hospital, No.199 Tung-Hwa North Road, Taipei, Taiwan, ROC.
Atherosclerosis. 2004 Jan;172(1):135-42. doi: 10.1016/j.atherosclerosis.2003.09.013.
Hepatic lipase (HL) is involved in the metabolism of several lipoproteins and plays a key role in reverse cholesterol transport. The aim of the current study was to test the statistical association between two HL gene promoter polymorphisms (HL-514C/T and HL-250G/A) and lipoprotein profiles in a Taiwanese-Chinese population.
A sample population of 716 Taiwanese-Chinese individuals was analyzed. DNA was extracted from the blood and genotypes were determined by polymerase chain reaction, restriction enzyme digestion, and agarose gel electrophoresis.
Analysis of the data revealed that these two polymorphisms are in strong linkage disequilibrium (D/D(max)=0.97, P<0.001). A significantly lower total cholesterol/HDL-C ratio was noted for carriers with the -514T and -250A alleles compared to non-carriers (P=0.007 and 0.004, respectively). A significant trend of the association was also found on the high levels of high-density-lipoprotein cholesterol (HDL-C) among carriers with the -514T and -250A alleles as opposed to that of non-carriers (P=0.030 and 0.023, respectively). Multivariate analysis has demonstrated that the effects of HL-514C/T and HL-250G/A polymorphisms on HDL-C levels were not affected by subjects' sex, body mass index, plasma triglyceride levels and the cholesterol ester transfer protein gene TaqIB polymorphism. Subgroup analysis on each sex has revealed that the two studied polymorphisms were significantly associated with HDL-C levels among males but not significant in women. The same association between obese and non-obese men was not consistent. The P-value of the respective polymorphisms on HDL-C levels were 0.012 and 0.002 among obese men, but not significant among non-obese men.
Analysis of our data revealed an independent association between the HL gene promoter polymorphisms and HDL-C levels in Taiwanese-Chinese. The data also suggests that the HL-514C/T and HL-250G/A polymorphisms interact with sex and obesity on HDL-C levels. The findings give clues for identifying high risk population in preventive medicine and clinical diagnosis. The subsequent impacts on treatment profiles and prognosis were derived from this study.
肝脂肪酶(HL)参与多种脂蛋白的代谢,在逆向胆固醇转运中起关键作用。本研究旨在检测台湾汉族人群中HL基因启动子的两个多态性位点(HL - 514C/T和HL - 250G/A)与脂蛋白谱之间的统计学关联。
对716名台湾汉族个体的样本群体进行分析。从血液中提取DNA,通过聚合酶链反应、限制性内切酶消化和琼脂糖凝胶电泳确定基因型。
数据分析显示这两个多态性位点处于强连锁不平衡状态(D/D(max)=0.97,P<0.001)。与非携带者相比,携带 - 514T和 - 250A等位基因的个体总胆固醇/高密度脂蛋白胆固醇(HDL - C)比值显著降低(分别为P = 0.007和0.004)。在携带 - 514T和 - 250A等位基因的个体中,与非携带者相比,高密度脂蛋白胆固醇(HDL - C)水平升高也存在显著的关联趋势(分别为P = 0.030和0.023)。多变量分析表明,HL - 514C/T和HL - 250G/A多态性对HDL - C水平的影响不受受试者性别、体重指数、血浆甘油三酯水平以及胆固醇酯转运蛋白基因TaqIB多态性的影响。按性别进行亚组分析显示,所研究的两个多态性位点与男性的HDL - C水平显著相关,但与女性无关。肥胖男性和非肥胖男性之间的相同关联并不一致。肥胖男性中各多态性位点对HDL - C水平的P值分别为0.012和0.002,但在非肥胖男性中不显著。
对我们数据的分析揭示了台湾汉族人群中HL基因启动子多态性与HDL - C水平之间的独立关联。数据还表明,HL - 514C/T和HL - 250G/A多态性在HDL - C水平上与性别和肥胖相互作用。这些发现为预防医学和临床诊断中识别高危人群提供了线索。本研究还得出了对治疗方案和预后的后续影响。