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Genetics of Variation in Serum Uric Acid and Cardiovascular Risk Factors in Mexican Americans

Department of Genetics (V.S.V., S.A.C., J.W.M., J.B., A.G.C.), Southwest Foundation for Biomedical Research, San Antonio, Texas 78227; George O' Brien Kidney Research Center (S.D.N., F.T., R.B., H.E.A., N.H.A.), Division of Nephrology and South Texas Veterans Health Care System, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229; and International Diabetes Institute (J.B.J.), Caulfield, Victoria 3162, Australia

Address all correspondence and requests for reprints to: V. Saroja Voruganti, Department of Genetics, Southwest Foundation for Biomedical Research, P.O. Box 760549, San Antonio, Texas 78245-0549. E-mail: svorugan{at}sfbrgenetics.org.

Background: Elevated serum uric acid is associated with several cardiovascular disease (CVD) risk factors such as hypertension, inflammation, endothelial dysfunction, insulin resistance, dyslipidemia, and obesity. However, the role of uric acid as an independent risk factor for CVD is not yet clear.

Objective: The aim of the study was to localize quantitative trait loci regulating variation in serum uric acid and also establish the relationship between serum uric acid and other CVD risk factors in Mexican Americans (n = 848; men = 310, women = 538) participating in the San Antonio Family Heart Study.

Methods: Quantitative genetic analysis was conducted using variance components decomposition method, implemented in the software program SOLAR.

Results: Mean ± SD of serum uric acid was 5.35 ± 1.38 mg/dl. Univariate genetic analysis showed serum uric acid and other CVD risk markers to be significantly heritable (P < 0.005). Bivariate analysis showed significant correlation of serum uric acid with body mass index, waist circumference, waist/hip ratio, total body fat, plasma insulin, serum triglycerides, high-density lipoprotein cholesterol, C-reactive protein, and granulocyte macrophage-colony stimulating factor (P < 0.05). A genome-wide scan for detecting quantitative trait loci regulating serum uric acid variation showed a significant logarithm of odds (LOD) score of 4.72 (empirical LOD score = 4.62; P < 0.00001) on chromosome 3p26. One LOD support interval contains 25 genes, of which an interesting candidate gene is chemokine receptor 2.

Summary: There is a significant genetic component in the variation in serum uric acid and evidence of pleiotropy between serum uric acid and other cardiovascular risk factors.

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