This Article Full Text Full Text (PDF) Supplemental Data Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Goodarzi, M. O. Articles by Rotter, J. I. Search for Related Content PubMed PubMed Citation Articles by Goodarzi, M. O. Articles by Rotter, J. I. Related Collections Lipid Cardiovascular Endocrinology Metabolism

Haplotypes in the Lipoprotein Lipase Gene Influence Fasting Insulin and Discovery of a New Risk Haplotype

Division of Endocrinology, Diabetes, and Metabolism (M.O.G.) and Medical Genetics Institute (M.O.G., K.D.T., X.G., J.C., Y.-D.I.C., J.I.R.), Cedars-Sinai Medical Center, Los Angeles, California 90048; Department of Medicine (M.O.G., Y.-D.I.C., J.I.R.), David Geffen School of Medicine at University of California, Los Angeles, California 90095; Department of Preventive Medicine and Biometrics (J.E.H.), University of Colorado Health Sciences Center, Denver, Colorado 80262; Department of Medicine (S.M.H.), University of Texas Health Sciences Center at San Antonio, San Antonio, Texas 78229; Department of Public Health Sciences (L.E.W.), Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157; and Department of Physiology and Biophysics (R.N.B.), Keck School of Medicine, University of Southern California, Los Angeles, California 90033

Address all correspondence and requests for reprints to: Mark O. Goodarzi, M.D., Ph.D., Cedars-Sinai Medical Center Division of Endocrinology, Diabetes, and Metabolism, 8700 Beverly Boulevard, Becker B-131, Los Angeles, California 90048. E-mail: mark.goodarzi{at}cshs.org.

Context: Prior studies of Mexican Americans described association of lipoprotein lipase (LPL) gene haplotypes with insulin sensitivity/resistance and atherosclerosis. The most common haplotype (haplotype 1) was protective, whereas the fourth most common haplotype (haplotype 4) conferred risk for insulin resistance and atherosclerosis.

Objective: In this study of Hispanics in the Insulin Resistance Atherosclerosis Study Family Study, we sought to replicate LPL haplotype association with insulin sensitivity/resistance.

Design: LPL haplotypes based on 12 single nucleotide polymorphisms were analyzed for association with indexes of insulin sensitivity and other metabolic and adiposity measures.

Setting: This study was conducted in the general community of San Antonio, Texas, and San Luis Valley, Colorado.

Participants: Participants in this study were 978 members of 86 Hispanic families.

Main Outcome Measures: LPL haplogenotype, metabolic phenotypes, and adiposity were measured in this study.

Results: The haplotype structure was identical with that observed in prior studies. Among 978 phenotyped subjects, haplotype 1 was associated with decreased fasting insulin (P = 0.01), and haplotype 4 was associated with increased fasting insulin (P = 0.02) and increased visceral fat mass (P = 0.002). Insulin sensitivity, derived from iv glucose tolerance testing, tended (P > 0.1) to be higher with haplotype 1 (S_I = 1.72) and lower with haplotype 4 (S_I=1.38). Haplotype 2 was associated with increases in fasting insulin, triglycerides (TGs), TG to high-density lipoprotein-cholesterol ratio, and apolipoprotein B (P = 0.01–0.04).

Conclusions: This study independently replicates our prior results of LPL haplotypes 1 and 4 as associated with measures of insulin sensitivity and resistance, respectively. Haplotype 4 may confer insulin resistance by increasing visceral fat. Haplotype 2 was identified as a new risk haplotype, suggesting the complex nature of LPL’s effect on features of the insulin resistance syndrome.

This article has been cited by other articles:

				M.-A. Cornier, D. Dabelea, T. L. Hernandez, R. C. Lindstrom, A. J. Steig, N. R. Stob, R. E. Van Pelt, H. Wang, and R. H. Eckel The Metabolic Syndrome Endocr. Rev., December 1, 2008; 29(7): 777 - 822. [Abstract] [Full Text] [PDF]