A major gene effect on the fasting insulin level and insulin resistance has been suggested in previous studies. Several candidate genes for insulin resistance in rare syndromes have been proposed. However, there has been limited success in finding genes for common forms of insulin resistance. There is accumulating evidence of a relationship between insulin resistance and a disturbance of free fatty acid (FFA) metabolism. The very-low-density lipoprotein (VLDL) receptor, which is associated with FFA metabolism, could serve as a possible candidate gene for insulin resistance. We performed linkage analyses between the VLDL receptor gene and fasting insulin and the homeostasis model assessment (HOMA) insulin resistance index (fasting insulin · fasting glucose/22.5) in 1,050 sibpairs participating in the phase II physical examination of the National Heart, Lung, and Blood Institute Family Heart Study (FHS). Data analyses were completed using the SIBPAL component of the SAGE software package (SAGE, Statistical Analysis for Genetic Epidemiology, Version 3.1; Computer program package available from the Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, 1997). We did not find evidence for linkage of the fasting insulin or the HOMA insulin resistance index with a polymorphic marker at the VLDL locus (P = .316 and .402, respectively). Adjustment of fasting insulin and the HOMA insulin resistance index for the body mass index (BMI) did not change the results (P = .319 and .472, respectively). In conclusion, no evidence was found for a linkage between a locus controlling the fasting insulin level or HOMA insulin resistance index and a VLDL polymorphism in the present study. Additional adjustment of fasting insulin or the HOMA insulin resistance index for the BMI did not change the linkage results significantly. (C) 2000 by W.B. Saunders Company.
Bibliographical noteFunding Information:
From the Division of Biostatistics, Washington University School of Medicine, St Louis, MO; Eccles Institute of Human Genetics and Division of Cardiovascular Genetics, University of Utah School of Medich~e, Salt Lake City, UZ," Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC; Department of Epidemiology and Department of Laboratory Medicine and Pathology, School of Public Health, University of Minnesota Medical School, Mimzeapolis, MN; and Section of Preventive Medicine and Epidemiology, Boston University Medical College, Boston, MA. Submitted March 8, 1999; acceptedAugust 5, 1999. Supported by National Heart, Lung, and Blood Institute Cooperative Agreement Grants No. NO1-HC-25104, NO1-HC-25105, NO1-HC-25106, NO1-HC-25107, NO1-HC-25108, and NOI-HC-25109. Address reprint requests to Yuling Hong, MD, PhD, Division of Biostatistics, Campus Box 8067, Washington University School of Medicine, 660 S Euclid Ave, St Louis, MO 63110. Copyright © 2000 by W.B. Saunders Company 0026-0495/00/4903-0002510.00/0
The SIBPAL subroutine program of SAGE Version 3.1 (1997) is supported by US Public Health Service Resource Grant No. I P41 RR03655 from the Division of Research Resources.