Genetic variation in the apolipoprotein H (β2-glycoprotein I) gene affects plasma apolipoprotein H concentrations

作     者：Mehdi, H Aston, CE Sanghera, DK Hamman, RF Kamboh, MI 

作者机构：Univ Pittsburgh Grad Sch Publ Hlth Dept Human Genet Pittsburgh PA 15261 USA Univ Colorado Hlth Sci Ctr Dept Prevent Med & Biometr Denver CO 80262 USA 

出 版 物：《HUMAN GENETICS》 (人类遗传学)

年 卷 期：1999年第105卷第1-2期

页      面：63-71页

核心收录：

学科分类：0710[理学-生物学] 0303[法学-社会学] 03[法学] 030303[法学-人类学] 

基　　金：NHLBI NIH HHS [HL 54900, HL 44672] Funding Source: Medline NIDDK NIH HHS [DK 30747] Funding Source: Medline 

主　　题：心磷脂质类/遗传学 胆固醇 HDL/遗传学 密码子 科罗拉多 欧洲大陆世系人群/遗传学 遗传变异 基因型 糖蛋白类/血液 糖蛋白类/遗传学 脂蛋白类 HDL/遗传学 多态现象 遗传 性别因素 血栓形成/遗传学 β2糖蛋白Ⅰ 成年人 老年人 女(雌)性 人类 男(雄)性 中年人 

摘      要：Apolipoprotein H (apoH, protein;APOH, gene) is a single chain glycoprotein that exists in plasma both in a free form and in combination with lipoprotein particles. ApoH has been implicated in several physiologic pathways, including lipid metabolism, coagulation, and the production of antiphospholipid antibodies. The wide range of interindividual variation in plasma apoH levels is thought to be under genetic control, but its molecular basis is unknown. APOH displays a common structural polymorphism with the occurrence of three common alleles (APOH*1, APOH*2, and APOH*3), the APOH*2 allele being the most frequent in all populations. The relationship between the APOH polymorphism and plasma apoH levels is unknown. In this study, we have determined the impact of this APOH polymorphism on apoH levels in 455 normoglycemic non-Hispanic Whites (220 men and 235 women) from the San Luis Valley, Colorado. Mean plasma apoH levels, determined by capture enzyme-linked immunosorbent assay, were 20.0 +/- 0.2 mg/dl (range: 3.4-31.2 mg/dl) with no significant difference between men and women. In women, but not in men, age had a significant effect on plasma apoH levels explaining 3.4% of its phenotypic variance. ApoH levels also correlated positively with cholesterol (P = 0.015), HDL-cholesterol (P = 0.044), and triglyceride (P = 0.037) in women, but not in men. An analysis of variance (ANOVA) of adjusted plasma apoH levels showed significant association with the APOH polymorphism in both men and women (P 0.0001), and the APOH polymorphism accounted for 11.4% and 13.6% of the variation in apoH levels in men and women, respectively. Compared with the APOH*1 and APOH*2 alleles, the APOH*3 allele was associated with significantly lower plasma apoH levels. At the molecular level, APOH*3 can be further subdivided into two distinct forms, called APOH*3(W) and APOH*3(B). The APOH*3(W) form is more common in US Whites and is the result of a missense mutation at codon 316. An ANOVA for the c