Factors of Insulin Resistance Syndrome–Related Phenotypes Are Linked to Genetic Locations on Chromosomes 6 and 7 in Nondiabetic Mexican-Americans
- Rector Arya1,
- John Blangero2,
- Ken Williams1,
- Laura Almasy2,
- Thomas D. Dyer2,
- Robin J. Leach3,
- Peter O’Connell4,
- Michael P. Stern1 and
- Ravindranath Duggirala1
- 1Department of Medicine, Division of Clinical Epidemiology, University of Texas Health Science Center, San Antonio, Texas
- 2Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas
- 3Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas
- 4Baylor College of Medicine Breast Center, Houston, Texas
Abstract
Insulin resistance syndrome (IRS)−related phenotypes, such as hyperinsulinemia, obesity-related traits, impaired glucose tolerance, dyslipidemia, and hypertension, tend to cluster into factors. We attempted to identify loci influencing the factors of IRS-related phenotypes using phenotypic data from 261 nondiabetic subjects distributed across 27 low-income Mexican-American extended families. Principal component factor analyses were performed using eight IRS-related phenotypes: fasting glucose (FG), fasting specific insulin (FSI), BMI, systolic blood pressure (SBP), diastolic blood pressure (DBP), HDL cholesterol, ln triglycerides (ln TGs), and leptin (LEP). The factor analysis yielded three factors: factor 1 (BMI, LEP, and FSI), factor 2 (DBP and SBP), and factor 3 (HDL and ln TG). We conducted multipoint variance components linkage analyses on these factors with the program SOLAR using a 10–15 cM map. We found significant evidence for linkage of factor 1 to two regions on chromosome 6 near markers D6S403 (logarithm of odds [LOD] = 4.2) and D6S264 (LOD = 4.9). We also found strong evidence for linkage of factor 3 to a genetic location on chromosome 7 between markers D7S479 and D7S471 (LOD = 3.2). In conclusion, we found substantial evidence for susceptibility loci on chromosomes 6 and 7 that appear to influence the factors representing the IRS-related phenotypes in Mexican-Americans.
Footnotes
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Address correspondence and reprint requests to Dr. Rector Arya, Division of Clinical Epidemiology, Department of Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78229-3900. E-mail: arya{at}uthscsa.edu.
Received for publication 31 July 2001 and accepted in revised form 4 December 2001.
DBP, diastolic blood pressure; FG, fasting glucose; FSI, fasting specific insulin; HDL-C, HDL cholesterol; IBD, identity by descent; IRS, insulin-resistance syndrome; LEP, leptin; ln TG, log-transformed TG values; LOD, logarithm of odds; PCFA, principal component factor analysis; SAFADS, San Antonio Family Diabetes Study; SBP, systolic blood pressure; TG, triglyceride.
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