Genomic loci with pleiotropic effects on coronary artery calcification

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• 作者：Stephen T. Turner ; Patricia A. Peyser ; Sharon L.R. Kardia ; Lawrence F. Bielak ; Patrick F. Sheedy III ; Eric Boerwinkle and Mariza de Andrade
• 关键词：Multivariate ; Genetic linkage ; Coronary artery disease ; Coronary artery calcification ; Obesity ; Blood pressure ; Pulse pressure ; High-density lipoprotein-cholesterol
• 刊名：Atherosclerosis
• 出版年：2006
• 出版时间：April 2006
• 年：2006
• 卷：185
• 期：2
• 页码：340-346
• 全文大小：171 K

文摘

We measured 381 genomewide markers and performed genetic linkage analyses in search of loci influencing coronary artery calcification (CAC), a measure of atherosclerosis determined by electron beam computed tomography, in 948 non-Hispanic white siblings (mean age [±standard deviation] = 59.6 ± 9.9 years; 73.7 % hypertensive). Measured risk factors for atherosclerosis included body mass index, pulse pressure, and high-density lipoprotein (HDL)-cholesterol. After adjustment for sex and age, the logarithm transformed measure of CAC was heritable (0.40 ± 0.08, P < 0.0001) and genetically correlated with body mass index (0.28, P < 0.001), pulse pressure (0.36, P < 0.001), and HDL-cholesterol (−0.19, P < 0.001). Univariate linkage analysis demonstrated evidence of linkage for CAC, defined by maximum LOD scores (MLS) ≥ 1.30, on chromosomes 1p, 4p, 5q, 7p, 13q, and 14q. Bivariate linkage analyses of CAC with each risk factor provided evidence of two regions with pleiotropic effects on CAC and HDL-cholesterol on chromosomes 4p16 (MLS = 3.03, P = 0.00084) and 9q12 (MLS = 3.21, P = 0.00056), and of a region with pleiotropic effects on CAC and body mass index on chromosome 17p11 (MLS = 3.04, P = 0.00082). Inasmuch as the chromosome 9 and 17 regions were not detected in the univariate linkage analysis for CAC, multivariate linkage analyses of CAC and genetically correlated risk factors may help localize genes for coronary atherosclerosis.