Genome-Wide Linkage Scan for Genes Influencing Plasma Triglyceride Levels in the Veterans Administration Genetic Epidemiology Study
- Dawn K. Coletta1,
- Jennifer Schneider2,
- Shirley L. Hu1,
- Thomas D. Dyer2,
- Sobha Puppala2,
- Vidya S. Farook2,
- Rector Arya3,
- Donna M. Lehman3,
- John Blangero2,
- Ralph A. DeFronzo1,4,
- Ravindranath Duggirala2 and
- Christopher P. Jenkinson1,2,4
- 1Division of Diabetes, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas
- 2Southwest Foundation for Biomedical Research, San Antonio, Texas
- 3Division of Clinical Epidemiology, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas
- 4South 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
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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.
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- Received April 10, 2008.
- Accepted October 7, 2008.
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