Friedlander Y, Austin M A, Newman B, Edwards K, Mayer-Davis E I, King M C
Department of Social Medicine, School of Public Health, Hadassah-University Hospital, Jerusalem, Israel.
Am J Hum Genet. 1997 Jun;60(6):1502-12. doi: 10.1086/515462.
Numerous studies have demonstrated genetic influences on levels of coronary heart disease (CHD) risk factors, but there also may be genetic effects on the intraindividual variation in these risk factors over time. Changes in risk factors are likely to reflect genetic-environmental interactions and may have important implications for understanding CHD risk. The present study examines the heritability of changes in CHD risk factors, using data from the two examinations by the Kaiser Permanente Women Twins Study, performed a decade apart. The sample consisted of 348 pairs of women twins who participated in both examinations, including 203 MZ pairs and 145 DZ pairs. Average ages at the two examinations were 41 and 51 years, respectively. By means of three different statistical analytic approaches, moderate heritability estimates were demonstrated for changes in LDL cholesterol (h2 = .25-.36) and in HDL cholesterol (h2 = .23-.58), some of which were statistically significant. Although small to moderate heritability estimates were found for systolic blood pressure (.18-.37; P < .05 for some estimates), no genetic influence on changes in diastolic blood pressure was detected. Based on longitudinal twin data in women, this study demonstrates a genetic influence on changes in both lipoprotein risk factors and systolic blood pressure over a decade. In addition to environmental factors, which clearly are operating, the effect of various "variability genes" may be acting independently of the genetic influences on the absolute levels of these risk factors. Both mapping the gene(s) underlying intraindividual variations in these CHD risk factors and understanding their function(s) could lead to targeted intervention strategies to reduce CHD risk among genetically susceptible individuals.
大量研究已证实基因对冠心病(CHD)危险因素水平有影响,但基因对这些危险因素随时间的个体内变化可能也有作用。危险因素的变化可能反映基因 - 环境相互作用,对理解冠心病风险可能具有重要意义。本研究利用凯撒医疗集团女性双胞胎研究相隔十年进行的两次检查的数据,考察了冠心病危险因素变化的遗传度。样本包括348对参加了两次检查的女性双胞胎,其中包括203对同卵双胞胎和145对异卵双胞胎。两次检查时的平均年龄分别为41岁和51岁。通过三种不同的统计分析方法,低密度脂蛋白胆固醇变化(h2 = 0.25 - 0.36)和高密度脂蛋白胆固醇变化(h2 = 0.23 - 0.58)显示出中等遗传度估计值,其中一些具有统计学意义。虽然收缩压变化的遗传度估计值较小到中等(0.18 - 0.37;部分估计值P < 0.05),但未检测到基因对舒张压变化有影响。基于女性的纵向双胞胎数据,本研究证明了基因对脂蛋白危险因素和收缩压在十年间变化的影响。除了明显起作用的环境因素外,各种“变异性基因”的作用可能独立于基因对这些危险因素绝对水平的影响。确定这些冠心病危险因素个体内变化背后的基因并了解其功能,都可能带来有针对性的干预策略,以降低遗传易感性个体的冠心病风险。