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Journal of Lipid Research, Vol. 49, 1034-1038, May 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

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^1,*,,,**,

^* Center for Cardiovascular Genetics, Cleveland Clinic Foundation, Cleveland, OH
Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH
Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, OH
^** Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH
Scripps Genomic Medicine, Scripps Research Institute, La Jolla, CA
Key Laboratory of Molecular Biophysics of the Ministry of Education and Center for Human Genome Research, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China

^* This research was supported by a National Heart, Lung, and Blood Institute Genotyping Service grant, by National Institutes of Health Grants P50 HL-77107 and P50 HL-81011, by the China National 863 Scientific Plan No. 2006AA02Z476, and by the National Basic Research Program of China (973 Program), Grants 2007CB512000, 2007CB512001, and 2007CB512002 (all to Q.K.W.).

Published, JLR Papers in Press, January 31, 2008.

¹ To whom correspondence should be addressed. e-mail: wangq2{at}ccf.org

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.

Supplementary key words genetics • linkage • coronary artery disease • myocardial infarction • metabolic syndrome

Abbreviations: ANGPTL3, angiopoietin-like 3; CAD, coronary artery disease; cM, centimorgan; LEPR, leptin receptor; LOD, logarithm of odds; MI, myocardial infarction; MIM, Online Mendelian Inheritance in Man; SCP2, sterol carrier protein 2; SNP, single nucleotide polymorphism; TG, triglyceride

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