Kamboh M I, Aston C E, Ferrell R E, Hamman R F
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, PA 15261.
Atherosclerosis. 1993 Jan 25;98(2):201-11. doi: 10.1016/0021-9150(93)90129-i.
The extent of apolipoprotein E (apo E) polymorphism and its effect on eight quantitative risk factors for coronary heart disease (total cholesterol; low density lipoprotein (LDL) cholesterol; total high density lipoprotein and its subfractions, HDL2 and HDL3; triglycerides; fasting glucose and fasting insulin) has been determined in 238 randomly selected Hispanics (120 males and 118 females) and 201 non-Hispanic whites (NHWs) (105 males and 96 females) from the San Luis Valley, Colorado. The frequencies for the E * 2, E * 3 and E * 4 alleles were 0.048, 0.853 and 0.099, respectively, in Hispanics and 0.080, 0.783 and 0.137, respectively, in NHWs. Relatively low frequency of the E * 2 and E * 4 alleles in Hispanics compared with NHWs is consistent with the genetic and anthropologic data that Hispanics have substantial Amerindian admixture. The impact of apo E polymorphism on each quantitative trait was estimated after adjusting for concomitant variables including age, cigarette smoking and body mass index in both genders and pre- or post-menopause status in females. The distribution of eight quantitative traits was analyzed among three common apo E phenotypes, 3-2, 3-3 and 4-3. In Hispanics, significant variability among apo E phenotypes was observed for total cholesterol (P = 0.001) in females only and the apo E polymorphism accounts for 12.4% variation in total cholesterol and 15.2% variation in LDL-cholesterol. In NHWs, significant mean differences among apo E phenotypes were observed for total cholesterol in both males (P = 0.007) and females (P = 0.0004). In NHW males and females, the apo E polymorphism explained 9.2% and 12.4%, respectively, of the variation in total cholesterol, and 15.1% and 6.6%, respectively, of the variation in LDL-cholesterol. In NHWs, borderline significance levels were also noted for phenotype specific differences in HDL2-cholesterol in males (P = 0.04) and females (P = 0.05), for total HDL cholesterol in females (P = 0.02) and HDL3-cholesterol in females (P = 0.06). While the estimated effects of the apo E polymorphism on quantitative traits differ somewhat between Hispanics and non-Hispanic whites, this probably reflects the overall difference in frequencies of the less common alleles in the Hispanics rather than a biological difference in the effects of these alleles on lipid metabolism.
在科罗拉多州圣路易斯谷随机选取了238名西班牙裔(120名男性和118名女性)和201名非西班牙裔白人(NHW,105名男性和96名女性),测定了载脂蛋白E(apo E)多态性的程度及其对冠心病八个定量风险因素的影响(总胆固醇;低密度脂蛋白(LDL)胆固醇;总高密度脂蛋白及其亚组分HDL2和HDL3;甘油三酯;空腹血糖和空腹胰岛素)。西班牙裔中E * 2、E * 3和E * 4等位基因的频率分别为0.048、0.853和0.099,NHW中分别为0.080、0.783和0.137。与NHW相比,西班牙裔中E * 2和E * 4等位基因的频率相对较低,这与西班牙裔有大量美洲印第安人血统的遗传和人类学数据一致。在对包括年龄、吸烟和体重指数(男女均有)以及女性绝经前或绝经后状态等伴随变量进行校正后,估计了apo E多态性对每个定量性状的影响。分析了三种常见apo E表型(3-2、3-3和4-3)中八个定量性状的分布。在西班牙裔中,仅在女性中观察到apo E表型之间总胆固醇存在显著差异(P = 0.001),apo E多态性占总胆固醇变异的12.4%和低密度脂蛋白胆固醇变异的15.2%。在NHW中,男性(P = 0.007)和女性(P = 0.0004)的apo E表型之间总胆固醇均观察到显著的平均差异。在NHW男性和女性中,apo E多态性分别解释了总胆固醇变异的9.2%和12.4%,以及低密度脂蛋白胆固醇变异的15.1%和6.6%。在NHW中,男性(P = 0.04)和女性(P = 0.05)的HDL2胆固醇、女性(P = 0.02)的总HDL胆固醇和女性(P = 0.06)的HDL3胆固醇的表型特异性差异也达到了临界显著水平。虽然apo E多态性对定量性状的估计影响在西班牙裔和非西班牙裔白人之间略有不同,但这可能反映了西班牙裔中较罕见等位基因频率的总体差异,而不是这些等位基因对脂质代谢影响的生物学差异。