Wittrup Hans H, Nordestgaard Børge G, Steffensen Rolf, Jensen Gorm, Tybjaerg-Hansen Anne
Department of Clinical Biochemistry, Herlev University Hospital, Copenhagen, Denmark.
Atherosclerosis. 2002 Nov;165(1):119-26. doi: 10.1016/s0021-9150(02)00183-1.
The G188E, D9N, and N291S mutations in LPL increase TG, reduce HDL cholesterol, and increase risk of ischemic heart disease. The common S447X mutation may have opposite effects. We genotyped 8451 women and men from the Danish general population, and 854 women and men with ischemic heart disease. Participants carrying G188E, D9N, or N291S were excluded. Compared with non-carriers, female heterozygotes and homozygotes presented with a 0.11 and 0.18 mmol/l decrease in plasma TG (P=0.001 and P=0.37) and a 0.07 and 0.03 mmol/l increase in HDL cholesterol (P=0.001 and P=0.99). Male heterozygotes and homozygotes presented with a 0.20 and 0.41 mmol decrease in plasma TG (P<0.001 and P=0.06), which was twice that in women, and a 0.05 and 0.17 mmol/l increase in plasma HDL cholesterol (P=0.02 and P=0.04), respectively. In meta-analyses by gender, the S447X mutation was associated with a significant l7% reduction in risk of ischemic heart disease in men (OR=0.83; P=0.01), whereas risk was unaffected in women (OR=0.97; P=0.98). The S447X mutation is associated with anti-atherogenic effects on TG and HDL cholesterol in both genders, and with a moderate protective effect on risk of ischemic heart disease in men.
脂蛋白脂肪酶（LPL）中的G188E、D9N和N291S突变会增加甘油三酯（TG）水平，降低高密度脂蛋白胆固醇（HDL胆固醇）水平，并增加缺血性心脏病风险。常见的S447X突变可能具有相反的作用。我们对来自丹麦普通人群的8451名女性和男性，以及854名患有缺血性心脏病的女性和男性进行了基因分型。携带G188E、D9N或N291S的参与者被排除在外。与非携带者相比，女性杂合子和纯合子的血浆TG分别降低了0.11和0.18 mmol/L（P = 0.001和P = 0.37），HDL胆固醇分别升高了0.07和0.03 mmol/L（P = 0.001和P = 0.99）。男性杂合子和纯合子的血浆TG分别降低了0.20和0.41 mmol（P<0.001和P = 0.06），是女性降低幅度的两倍，血浆HDL胆固醇分别升高了0.05和0.17 mmol/L（P = 0.02和P = 0.04）。在按性别进行的荟萃分析中，S447X突变与男性缺血性心脏病风险显著降低17%相关（OR = 0.83；P = 0.01），而女性风险未受影响（OR = 0.97；P = 0.98）。S447X突变与两性的TG和HDL胆固醇的抗动脉粥样硬化作用相关，并且对男性缺血性心脏病风险具有中等程度的保护作用。
