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Genetics

Genome-Wide Scans Reveal Quantitative Trait Loci on 8p and 13q Related to Insulin Action and Glucose Metabolism

The San Antonio Family Heart Study

  1. Guowen Cai12,
  2. Shelley A. Cole1,
  3. Jeanne H. Freeland-Graves2,
  4. Jean W. MacCluer1,
  5. John Blangero1 and
  6. Anthony G. Comuzzie1
  1. 1Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas
  2. 2Department of Human Ecology, Nutrition Division, University of Texas at Austin, Austin, Texas
  1. Address correspondence and reprint requests to Anthony G. Comuzzie, Department of Genetics Southwest Foundation for Biomedical Research, 7620 NW Loop 410, San Antonio, TX 78227-5301. E-mail: agcom{at}darwin.sfbr.org
Diabetes 2004 May; 53(5): 1369-1374. https://doi.org/10.2337/diabetes.53.5.1369
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The San Antonio Family Heart Study

Abstract

Type 2 diabetes is a complex disease that arises from physiological disruptions of the body’s sensitivity to insulin and ability to metabolize glucose. Multipoint linkage analyses for insulin sensitivity phenotypes were conducted in 1,280 Mexican Americans from 41 families who participated in the San Antonio Family Heart Study. A significant linkage signal (logarithm of odds [LOD] = 2.98) affecting corrected insulin response to glucose was detected on chromosome 13q between D13787 and D13S252, in the region where the MODY-4 gene has previously been mapped. Another signal on chromosome 13 was observed at D13S285 (LOD = 1.86), where the insulin receptor substrate 2 gene resides. Significant linkage (LOD = 3.09) for insulin response to glucose was found on chromosome 8 between D8S1130 and D8S1106, near the lipoprotein lipase and macrophage scavenger receptor genes. Multipoint analysis of abdominal skinfold with an LOD of 2.68 showed signals in the same region. There was also suggestive evidence for linkage of quantitative insulin sensitivity check index and fasting glucose to a previously reported location at D9S301 (LOD = 2.19). These results indicate that chromosomal locations on 8p and 13q might harbor genes that affect a variety of insulin- and glucose-related phenotypes that contribute to the observed variations in these important risk factors for diabetes in Mexican Americans.

  • CIR, corrected insulin response
  • HOMA-IR, homeostasis model assessment of insulin resistance index
  • IBD, identity-by-descent
  • IPF-1, insulin promotor factor-1
  • IRG, insulin response to glucose
  • LOD, logarithm of odds
  • MODY, maturity-onset diabetes of the young
  • NPL, nonparametric linkage
  • QTL, quantitative trait locus
  • QUICKI, quantitative insulin sensitivity check index

Footnotes

    • Accepted January 26, 2004.
    • Received September 9, 2003.
  • DIABETES
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Genome-Wide Scans Reveal Quantitative Trait Loci on 8p and 13q Related to Insulin Action and Glucose Metabolism
Guowen Cai, Shelley A. Cole, Jeanne H. Freeland-Graves, Jean W. MacCluer, John Blangero, Anthony G. Comuzzie
Diabetes May 2004, 53 (5) 1369-1374; DOI: 10.2337/diabetes.53.5.1369

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Genome-Wide Scans Reveal Quantitative Trait Loci on 8p and 13q Related to Insulin Action and Glucose Metabolism
Guowen Cai, Shelley A. Cole, Jeanne H. Freeland-Graves, Jean W. MacCluer, John Blangero, Anthony G. Comuzzie
Diabetes May 2004, 53 (5) 1369-1374; DOI: 10.2337/diabetes.53.5.1369
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