Genome-Wide Linkage Scan for Genes Influencing Plasma Triglyceride Levels in the Veterans Administration Genetic Epidemiology Study

• Published in: Diabetes (New York, N.Y.) Vol. 58; no. 1; pp. 279 - 284
• Main Authors: COLETTA, Dawn K, SCHNEIDER, Jennifer, DUGGIRALA, Ravindranath, JENKINSON, Christopher P, HU, Shirley L, DYER, Thomas D, PUPPALA, Sobha, FAROOK, Vidya S, ARYA, Rector, LEHMAN, Donna M, BLANGERO, John, DEFRONZO, Ralph A
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.01.2009
• Subjects: Biological and medical sciences; Cardiovascular disease; Chromosome Mapping - methods; Chromosomes; Chromosomes, Human, Pair 12 - genetics; Demographic aspects; Diabetes; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - ethnology; Diabetes Mellitus, Type 2 - genetics; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Epidemiology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Family Health; Female; Genetic aspects; Genetic Predisposition to Disease - genetics; Genetics; Genome-Wide Association Study - methods; Genomes; Genotype; Health aspects; Hispanic Americans; Humans; Influence; Insulin resistance; Lod Score; Male; Medical sciences; Metabolic syndrome X; Metabolism; Mexican Americans; Mexican Americans - genetics; Mexican Americans - statistics & numerical data; Microsatellite Repeats - genetics; Middle Aged; Obesity; Phenotype; Plasma; Research design; Texas - epidemiology; Triglycerides; Triglycerides - blood; Veterans; Texas; United States; Endocrinopathy; Gene; Diabetes mellitus; Genetic linkage; Lipids; Genetics; Genome; Triglyceride; Epidemiology
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db08-0491

Genome-Wide Linkage Scan for Genes Influencing Plasma Triglyceride Levels in the Veterans Administration Genetic Epidemiology Study Dawn K. Coletta 1 , Jennifer Schneider 2 , Shirley L. Hu 1 , Thomas D. Dyer 2 , Sobha Puppala 2 , Vidya S. Farook 2 , Rector Arya 3 , Donna M. Lehman 3 , John Blangero 2 , Ralph A. DeFronzo 1 4 , Ravindranath Duggirala 2 and Christopher P. Jenkinson 1 2 4 1 Division of Diabetes, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas 2 Southwest Foundation for Biomedical Research, San Antonio, Texas 3 Division of Clinical Epidemiology, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas 4 South Texas Veterans Health Care System, San Antonio, Texas Corresponding author: Dawn K. Coletta, dawn.coletta{at}asu.edu Abstract OBJECTIVE— Elevated plasma triglyceride concentration is a component of the insulin resistance syndrome and is commonly associated with type 2 diabetes, obesity, and coronary heart disease. The goal of our study was to perform a genome-wide linkage scan to identify genetic regions that influence variation in plasma triglyceride levels in families that are enriched with individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS— We used phenotypic and genotypic data from 1,026 individuals distributed across 294 Mexican-American families, who were ascertained for type 2 diabetes, from the Veterans Administration Genetic Epidemiology Study (VAGES). Plasma triglyceride values were transformed, and a variance-components technique was used to conduct multipoint linkage analysis. RESULTS— After adjusting for the significant effects of sex and BMI, heritability for plasma triglycerides was estimated as 46 ± 7% ( P < 0.0001). Multipoint linkage analysis yielded the strongest evidence for linkage of plasma triglycerides near marker D12S391 on chromosome 12p (logarithm of odds [LOD] = 2.4). Our linkage signal on chromosome 12p provides independent replication of a similar finding in another Mexican-American sample from the San Antonio Family Diabetes Study (SAFDS). Combined multipoint linkage analysis of the VAGES and SAFDS data yielded significant evidence for linkage of plasma triglycerides to a genetic location between markers GATA49D12 and D12S391 on 12p (LOD = 3.8, empirical P value = 2.0 × 10 −5 ). This region on 12p harbors the gene-encoding adiponectin receptor 2 ( AdipoR2 ), where we previously have shown that multiple single nucleotide polymorphisms are associated with plasma triglyceride concentrations in the SAFDS. In the present study, we provided suggestive evidence in favor of association for rs929434 with triglyceride concentrations in the VAGES. CONCLUSIONS— Collectively, these results provide strong evidence for a major locus on chromosome 12p that influences plasma triglyceride levels in Mexican Americans. Footnotes Published ahead of print at http://diabetes.diabetesjournals.org on 17 October 2008. D.K.C. is currently affiliated with the Center for Metabolic Biology, College of Liberal Arts and Sciences, Arizona State University, Tempe, Arizona. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted October 7, 2008. Received April 10, 2008. DIABETES