A Genome Scan for Fasting Insulin and Fasting Glucose Identifies a Quantitative Trait Locus on Chromosome 17p

The Insulin Resistance Atherosclerosis Study (IRAS) Family Study

  1. Stephen S. Rich1,
  2. Donald W. Bowden2,
  3. Steven M. Haffner3,
  4. Jill M. Norris4,
  5. Mohammed F. Saad5,
  6. Braxton D. Mitchell6,
  7. Jerome I. Rotter7,
  8. Carl D. Langefeld1,
  9. Catherine C. Hedrick8,
  10. Lynne E. Wagenknecht1 and
  11. Richard N. Bergman9
  1. 1Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina
  2. 2Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina
  3. 3Department of Medicine, University of Texas Health Sciences Center at San Antonio, San Antonio, Texas
  4. 4Department of Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Denver, Colorado
  5. 5Division of Clinical Epidemiology, University of California at Los Angeles, Los Angeles, California
  6. 6Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland
  7. 7Medical Genetics Institute, Steven Spielberg Pediatric Research Center, Cedars-Sinai Burns and Allen Research Institute, Los Angeles, California
  8. 8Division of Endocrinology and Metabolism, University of Virginia Health Systems, Charlottesville, Virginia
  9. 9Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California
  1. Address correspondence and reprint requests to Stephen S. Rich, PhD, Department of Public Health Sciences, Wake Forest University School of Medicine, 3rd Floor MRI Center, Winston-Salem, NC 27157. E-mail: srich{at}wfubmc.edu

Abstract

Plasma insulin and glucose concentrations are important quantitative phenotypes related to diabetes and the metabolic syndrome. Reports purporting to identify quantitative trait loci (QTLs) that contribute to the variation in fasting insulin and glucose concentrations are discrepant. As part of the Insulin Resistance Atherosclerosis Study (IRAS) Family Study, a genome scan was performed in African-American (n = 42) and Hispanic (n = 90) extended families to identify regions that may contain positional candidate genes for fasting insulin and fasting glucose (n = 1,604 subjects). There was significant evidence for linkage of fasting insulin to the short arm of chromosome 17 (logarithm of odds [LOD] = 3.30; 54 cM between D17S1294 and D17S1299, P = 1.0 × 10−4). The strongest evidence for linkage over all pedigrees for fasting glucose was also observed in this region (LOD = 1.44; 58 cM, P = 9.9 × 10−3). The results of this study provide impetus for future positional cloning of QTLs regulating insulin and glucose levels. Identifying genes in these regions should provide insight into the nature of genetic factors regulating plasma glucose and insulin concentrations.

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This Article

  1. doi: 10.2337/diabetes.54.1.290 Diabetes January 2005 vol. 54 no. 1 290-295
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