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Journal of Lipid Research, Vol. 45, 610-615, April 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Genetic determinants of obesity-related lipid traits

Gabriele E. Sonnenberg^1,*, Glenn R. Krakower^*, Lisa J. Martin, Michael Olivier^*, Anne E. Kwitek^*, Anthony G. Comuzzie, John Blangero and Ahmed H. Kissebah^*

^* Division of Endocrinology, Metabolism and Clinical Nutrition, Department of Medicine and Human Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI
Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX

¹ To whom correspondence should be addressed. e-mail: gsonnen{at}mcw.edu

In our ongoing effort to identify genes influencing the biological pathways that underlie the metabolic disturbances associated with obesity, we performed genome-wide scanning in 2,209 individuals distributed over 507 Caucasian families to localize quantitative trait loci (QTLs), which affect variation of plasma lipids. Pedigree-based analysis using a quantitative trait variance component linkage method that localized a QTL on chromosome 7q35-q36, which linked to variation in levels of plasma triglyceride [TG, logarithm of odds (LOD) score = 3.7] and was suggestive of linkage to LDL-cholesterol (LDL-C, LOD = 2.2). Covariates of the TG linkage included waist circumference, fasting insulin, and insulin:glucose, but not body mass index or hip circumference. Plasma HDL-cholesterol (HDL-C) levels were suggestively linked to a second QTL on chromosome 12p12.3 (LOD = 2.6). Five other QTLs with lower LOD scores were identified for plasma levels of LDL-C, HDL-C, and total cholesterol.

These newly identified loci likely harbor genetic elements that influence traits underlying lipid adversities associated with obesity.

Abbreviations: apoB, apolipoprotein B; BMI, body mass index; cM, centiMorgan; eNOS, endothelial nitric oxide synthase; HDL-C, HDL-cholesterol; IBD, identity-by-descent; LDL-C, LDL-cholesterol; LOD, logarithm of odds; NO, nitric oxide; QTLs, quantitative trait loci; STRP, short tandem repeat polymorphism; TG, triglyceride; TNF, tumor necrosis factor; total-C, total cholesterol

Supplementary key words linkage analysis • triglycerides • obesity • lipid profiles • high density lipoprotein cholesterol

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