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Lipoprotein Candidate Genes for Multivariate Factors of the Insulin Resistance Syndrome: A Sib-pair Linkage Analysis in Women Twins

Published online by Cambridge University Press:  21 February 2012

K.L. Edwards*
Affiliation:
Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA. keddy@u.washington.edu
P.J. Talmud
Affiliation:
Division of Cardiovascular Genetics, Department of Medicine, Rayne Institute, University College London, London.
B. Newman
Affiliation:
School of Public Health, Queensland University of Technology, Brisbane, Queensland, Australia.
R.M. Krauss
Affiliation:
Department of Molecular and Nuclear Medicine, Life Sciences Division, Ernest Orlando Lawrence Berkeley National Laboratory, Berkeley, CA.
M.A. Austin
Affiliation:
Institute for Public Health Genetics, School of Public Health and Community Medicine, University of Washington, Seattle, WA.
*
*Address for Correspondence: Karen L. Edwards, Ph.D., Department of Epidemiology, Box 357236, School of Public Health and Community Medicine, University of Washington, Seattle, WA 98195, USA.

Abstract

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The insulin resistance syndrome (IRS) is characterized by a combination of interrelated coronary heart disease risk factors, including low high-density lipoprotein cholesterol (HDLC) levels, obesity and increases in triglyceride (TG), systolic and diastolic blood pressure (BP), small low-density lipoprotein particles (LDL-size), and fasting and postload plasma insulin and glucose. Using factor analysis, we previously identified multivariate factors based on data from women participating in the Kaiser Permanente Women Twins Study: 1) Weight/Fat, 2) Insulin/Glucose, 3) Lipids, and 4) BP. The purpose of this study is to evaluate evidence for genetic linkage between the multivariate factors and candidate genes. Quantitative sib-pair analysis based on the factor scores with markers for 9 candidate genes was carried out based on data from 126 pairs of dizygotic (DZ) women twins from the second exam of the Kaiser Permanente Women Twins study. Suggestive evidence for linkage was found for the Weight/fat factor and the Apo E gene (p = 0.01), and stronger evidence for linkage with the Lipid factor and the cholesterol ester transfer protein (p = 0.002) gene. Therefore, the CETP gene appears to influence covariation in LDL size, TG, and HDL, and may account for a portion of the well-established statistical and metabolic associations observed between these risk factors.

Type
Articles
Copyright
Copyright © Cambridge University Press 2001