Submitted on December 11, 2007
Revised on January 22, 2008
Accepted on January 30, 2008
Identification of a novel locus for triglyceride on chromosome 1p31-32 in families with premature CAD and MI
Sara Bretschger Seidelmann, Lin Li, Gong-Qing Shen, Eric J. Topol, and Qing Kenneth Wang
Department of Molecular Cardiology, Cleveland Clinic, Cleveland, OH 44195
Corresponding Author: wangq2{at}ccf.org
An elevated 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 employed 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 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 triglyceride on chromosome 1p31-32. Future studies of the candidate genes at the 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.
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