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调节γ-谷氨酰转移酶和白蛋白血浆水平的数量性状位点及其与心血管危险因素的遗传相关性。

Quantitative loci regulating plasma levels of gamma glutamyl transferase and albumin and their genetic correlations with cardiovascular risk factors.

作者信息

Bose Tanushree, Voruganti V Saroja, Tejero M Elizabeth, Proffitt J Michael, Cox Laura A, VandeBerg John L, Mahaney Michael C, Rogers Jeffrey, Freeland-Graves Jeanne H, Cole Shelley A, Comuzzie Anthony G

机构信息

Division of Nutritional Sciences, Department of Human Ecology, The University of Texas at Austin,Austin, Texas 78712, USA.

出版信息

Exp Biol Med (Maywood). 2009 Dec;234(12):vi, 1519-24. doi: 10.3181/0903-RM-115.

Abstract

gamma Glutamyl transferase (GGT) and albumin (ALB) are two markers of liver function. These two proteins have been associated with non-alcoholic fatty liver disease and cardiovascular disease. The objectives of this study were to explore the genetic factors that influence variation in the plasma levels of GGT and ALB and to evaluate their genetic correlations with cardiovascular risk factors. Baboons from the Southwest National Primate Research Center at the Southwest Foundation for Biomedical Research, San Antonio, TX, were used as an animal model. The baboons were fed a standard monkey chow diet ad libitum. Fasting plasma concentrations of GGT, ALB, triglycerides, total cholesterol and LDL cholesterol were measured in 350 pedigreed adult baboons by standard assay procedures. A maximum likelihood-based variance decomposition approach implemented in the computer program SOLAR was used to conduct genetic analyses. The heritabilities of GGT (h(2) = 0.55; P < 0.0001) and ALB (h(2) = 0.42; P < 0.01) were significant. No statistically significant associations were found between GGT and the cardiovascular-related phenotypes. Genetic correlations between ALB and total cholesterol, LDL cholesterol and triglycerides were significant. A QTL (LOD = 2.8) for GGT plasma levels was identified on the baboon homologue of human chromosome 22 between markers D22S304 and D22S280. A QTL (LOD = 2.3) near marker D10S1432 was detected on the baboon homologue of human chromosome 10 for ALB. These results imply that variations in the plasma levels of GGT and ALB are under significant genetic regulation and that a common genetic component influences ALB and cardiovascular risk factor phenotypes.

摘要

γ-谷氨酰转移酶(GGT)和白蛋白(ALB)是肝功能的两项指标。这两种蛋白质与非酒精性脂肪性肝病和心血管疾病有关。本研究的目的是探索影响GGT和ALB血浆水平变异的遗传因素,并评估它们与心血管危险因素的遗传相关性。位于德克萨斯州圣安东尼奥市西南生物医学研究基金会的西南国家灵长类动物研究中心的狒狒被用作动物模型。这些狒狒随意进食标准猴粮。通过标准检测程序,在350只成年纯种狒狒中测量了GGT、ALB、甘油三酯、总胆固醇和低密度脂蛋白胆固醇的空腹血浆浓度。使用计算机程序SOLAR中实施的基于最大似然的方差分解方法进行遗传分析。GGT(h(2) = 0.55;P < 0.0001)和ALB(h(2) = 0.42;P < 0.01)的遗传力显著。未发现GGT与心血管相关表型之间存在统计学上的显著关联。ALB与总胆固醇、低密度脂蛋白胆固醇和甘油三酯之间的遗传相关性显著。在人类22号染色体的狒狒同源物上,标记D22S304和D22S280之间鉴定出一个GGT血浆水平的QTL(LOD = 2.8)。在人类10号染色体的狒狒同源物上,标记D10S1432附近检测到一个ALB的QTL(LOD = 2.3)。这些结果表明,GGT和ALB血浆水平的变异受到显著的遗传调控,并且一个共同的遗传成分影响ALB和心血管危险因素表型。

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