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7号染色体7q32.3-qter区域存在影响甘油三酯/高密度脂蛋白胆固醇比值的基因的证据:弗雷明汉心脏研究中的全基因组扫描。

Evidence for a gene influencing the TG/HDL-C ratio on chromosome 7q32.3-qter: a genome-wide scan in the Framingham study.

作者信息

Shearman A M, Ordovas J M, Cupples L A, Schaefer E J, Harmon M D, Shao Y, Keen J D, DeStefano A L, Joost O, Wilson P W, Housman D E, Myers R H

机构信息

Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA,

出版信息

Hum Mol Genet. 2000 May 22;9(9):1315-20. doi: 10.1093/hmg/9.9.1315.

Abstract

Some studies show that plasma triglyceride (TG) levels are a significant independent risk factor for cardiovascular disease (CVD). TG levels are inversely correlated with high density lipoprotein cholesterol (HDL-C) levels, and their metabolism may be closely interrelated. Therefore, the TG/HDL-C ratio may be a relevant CVD risk factor. Our analysis of families in the Framingham Heart Study gave a genetic heritability estimate for log(TG) of 0.40 and for log(TG/HDL-C) of 0.49, demonstrating an important genetic component for both. A 10 cM genome-wide scan for log(TG) level and log(TG/HDL-C) was carried out for the largest 332 extended families of the Framingham Heart Study (1702 genotyped individuals). The highest multipoint variance component LOD scores obtained for both log(TG) and log(TG/HDL-C) were on chromosome 7 (at 155 cM), where the results for the two phenotypes were 1.8 and 2.5, respectively. The 7q32.3-qter region contains several candidate genes. Four other regions with multipoint LOD scores greater than one were identified on chromosome 3 [LOD score for log(TG/HDL-C) = 1.8 at 140 cM], chromosome 11 [LOD score for log(TG/HDL-C) = 1.1 at 125 cM], chromosome 16 [LOD score for log(TG) = 1.5 at 70 cM, LOD score for log(TG/HDL-C) = 1.1 at 75 cM] and chromosome 20 [LOD score for log(TG/HDL-C) = 1.7 at 35 cM, LOD score for log(TG) = 1.3 at 40 cM]. These results identify loci worthy of further study.

摘要

一些研究表明,血浆甘油三酯(TG)水平是心血管疾病(CVD)的一个重要独立危险因素。TG水平与高密度脂蛋白胆固醇(HDL-C)水平呈负相关,且它们的代谢可能密切相关。因此,TG/HDL-C比值可能是一个相关的CVD危险因素。我们对弗雷明汉心脏研究中的家族进行分析,得出log(TG)的遗传度估计值为0.40,log(TG/HDL-C)的遗传度估计值为0.49,表明二者都有重要的遗传成分。对弗雷明汉心脏研究中最大的332个大家庭(1702名基因分型个体)进行了全基因组扫描,扫描范围为log(TG)水平和log(TG/HDL-C),扫描间距为10厘摩(cM)。log(TG)和log(TG/HDL-C)获得的最高多点方差成分对数优势分数(LOD)均位于7号染色体上(155 cM处),两种表型的结果分别为1.8和2.5。7q32.3-qter区域包含几个候选基因。在3号染色体[140 cM处log(TG/HDL-C)的LOD分数 = 1.8]、11号染色体[125 cM处log(TG/HDL-C)的LOD分数 = 1.1]、16号染色体[70 cM处log(TG)的LOD分数 = 1.5,75 cM处log(TG/HDL-C)的LOD分数 = 1.1]和20号染色体[35 cM处log(TG/HDL-C)的LOD分数 = 1.7,40 cM处log(TG)的LOD分数 = 1.3]上还发现了其他四个多点LOD分数大于1的区域。这些结果确定了值得进一步研究的基因座。

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