Seidelmann Sara Bretschger, Li Lin, Shen Gong-Qing, Topol Eric J, Wang Qing Kenneth
Center for Cardiovascular Genetics, Cleveland Clinic Foundation, Cleveland, OH, USA.
J Lipid Res. 2008 May;49(5):1034-8. doi: 10.1194/jlr.M700576-JLR200. Epub 2008 Jan 31.
An increased plasma triglyceride (TG) level is associated with coronary artery disease (CAD) and myocardial infarction (MI) and is a key characteristic of the metabolic syndrome. Here, we used a genome-wide linkage scan to identify a novel genetic locus that influences the plasma TG level. We genotyped 714 persons in 388 multiplex Caucasian families with premature CAD and MI with 408 polymorphic microsatellite markers that cover the entire human genome. The genome-wide scan identified positive linkage for the quantitative TG trait to a novel locus on chromosome 1p31-32 [peak single-point logarithm of odds (LOD) = 3.57, peak multipoint LOD = 3.12]. For single-point linkage analysis, two markers, D1S1728 and D1S551, showed LOD scores of 2.42 and 3.57, respectively. For multipoint linkage analysis, three markers, D1S3736, D1S1728, and D1S551, showed LOD scores of 2.43, 3.03, and 3.12, respectively. No other chromosomal regions showed a LOD score of >2.2. This study identifies a new genetic locus for TG on chromosome 1p31-32. Future studies of the candidate genes at this locus will identify a specific gene influencing the TG, which will provide insights into novel regulatory mechanisms of TG metabolism and may be important for the development of therapies to prevent CAD.
血浆甘油三酯（TG）水平升高与冠状动脉疾病（CAD）和心肌梗死（MI）相关，是代谢综合征的一个关键特征。在此，我们使用全基因组连锁扫描来识别一个影响血浆TG水平的新基因座。我们对388个患有早发性CAD和MI的白种人多重家庭中的714人进行基因分型，使用覆盖整个人类基因组的408个多态性微卫星标记。全基因组扫描确定了定量TG性状与1号染色体1p31 - 32上一个新基因座的正向连锁[峰值单点优势对数（LOD）= 3.57，峰值多点LOD = 3.12]。对于单点连锁分析，两个标记D1S1728和D1S551的LOD分数分别为2.42和3.57。对于多点连锁分析，三个标记D1S3736、D1S1728和D1S551的LOD分数分别为2.43、3.03和3.12。没有其他染色体区域的LOD分数>2.2。本研究在1号染色体1p31 - 32上确定了一个新的TG基因座。对该基因座候选基因的进一步研究将鉴定出一个影响TG的特定基因，这将为TG代谢的新调控机制提供见解，并且可能对预防CAD的治疗方法的开发具有重要意义。
