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PLoS Genetics:一种基因变异可能导致早期冠心病

来源:新华网 2009-01-03 20:08

美国杜克大学医学中心的研究人员1月2日报告说,一种特殊基因变异可能增加人罹患早期冠心病的风险。

研究人员在2日出版的《公共科学图书馆·遗传学》(PLoS Genetics)杂志网络版上发表论文说,他们数年前就发现早期冠心病具有遗传性,但直到最近才证实一种神经肽Y基因的变异与这种遗传性相关。神经肽Y基因位于人类7号染色体上,负责编码产生一种影响饮食的重要蛋白质神经肽Y。

研究人员对参与杜克大学一个医学研究项目的1000个家庭进行分析后发现,神经肽Y基因变异与冠心病发作存在较强的相关性,这种联系在年龄小于37岁的冠心病患者中尤其明显。

早期冠心病一般指心肌缺血的隐性冠心病和心绞痛,表现为或有胸闷、胸部压迫感和紧束感,或心前区隐隐作痛,或无症状。早期冠心病在年轻患者中很难确诊。

研究人员说,他们的研究将有望帮助专家在早期冠心病患者病情发作前作出诊断。对这类患者进行有效的早期治疗,可以阻止病情进一步发展。(生物谷Bioon.com)

生物谷推荐原始出处:

PLoS Genet 5(1): e1000318. doi:10.1371/journal.pgen.1000318

Neuropeptide Y Gene Polymorphisms Confer Risk of Early-Onset Atherosclerosis

Svati H. Shah1,2*, Neil J. Freedman1, Lisheng Zhang1, David R. Crosslin2, David H. Stone3, Carol Haynes2, Jessica Johnson2, Sarah Nelson2, Liyong Wang4, Jessica J. Connelly2, Michael Muehlbauer5, Geoffrey S. Ginsburg1,6, David C. Crossman7, Christopher J. H. Jones8, Jeffery Vance4, Michael H. Sketch, Jr1, Christopher B. Granger1, Christopher B. Newgard5, Simon G. Gregory2, Pascal J. Goldschmidt-Clermont4, William E. Kraus1, Elizabeth R. Hauser2

1 Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America, 2 Center for Human Genetics, Duke University Medical Center, Durham, North Carolina, United States of America, 3 Department of Surgery, Duke University, Durham, North Carolina, United States of America, 4 Miller School of Medicine, University of Miami, Miami, Florida, United States of America, 5 Sarah W. Stedman Center for Nutrition and Metabolism at Duke, Durham, North Carolina, United States of America, 6 Duke Institute for Genome Sciences and Policy, Durham, North Carolina, United States of America, 7 University of Sheffield School of Medicine, Sheffield, United Kingdom, 8 The Wales Heart Research Institute, Cardiff, United Kingdom

Neuropeptide Y (NPY) is a strong candidate gene for coronary artery disease (CAD). We have previously identified genetic linkage to familial CAD in the genomic region of NPY. We performed follow-up genetic, biostatistical, and functional analysis of NPY in early-onset CAD. In familial CAD (GENECARD, N = 420 families), we found increased microsatellite linkage to chromosome 7p14 (OSA LOD = 4.2, p = 0.004) in 97 earliest age-of-onset families. Tagged NPY SNPs demonstrated linkage to CAD of a 6-SNP block (LOD = 1.58–2.72), family-based association of this block with CAD (p = 0.02), and stronger linkage to CAD in the earliest age-of-onset families. Association of this 6-SNP block with CAD was validated in: (a) 556 non-familial early-onset CAD cases and 256 controls (OR 1.46–1.65, p = 0.01–0.05), showing stronger association in youngest cases (OR 1.84–2.20, p = 0.0004–0.09); and (b) GENECARD probands versus non-familial controls (OR 1.79–2.06, p = 0.003–0.02). A promoter SNP (rs16147) within this 6-SNP block was associated with higher plasma NPY levels (p = 0.04). To assess a causal role of NPY in atherosclerosis, we applied the NPY1-receptor–antagonist BIBP-3226 adventitially to endothelium-denuded carotid arteries of apolipoprotein E-deficient mice; treatment reduced atherosclerotic neointimal area by 50% (p = 0.03). Thus, NPY variants associate with atherosclerosis in two independent datasets (with strong age-of-onset effects) and show allele-specific expression with NPY levels, while NPY receptor antagonism reduces atherosclerosis in mice. We conclude that NPY contributes to atherosclerosis pathogenesis.

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