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Genome Scan for Determinants of Serum Uric Acid Variability

Subrata D. Nath^*, V. Saroja Voruganti, Nedal H. Arar^*, Farook Thameem^*, Juan C. Lopez-Alvarenga, Richard Bauer^*, John Blangero, Jean W. MacCluer, Anthony G. Comuzzie and Hanna E. Abboud^*

^* Department of Medicine, University of Texas Health Science Center at San Antonio, and Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas

Correspondence: Dr. Hanna E. Abboud, Division of Nephrology, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229. Phone: 210-567-4700; Fax: 210-567-4712; E-mail: abboud{at}uthscsa.edu

Received for publication April 9, 2007. Accepted for publication July 24, 2007.

Elevated serum uric acid level is associated with obesity, insulin resistance, diabetes, nephropathy, and hypertension. Epidemiologic studies suggest that serum uric acid levels are heritable. We sought to identify chromosomal regions harboring quantitative trait loci that influence serum uric acid in Mexican Americans using data from 644 participants in the San Antonio Family Heart Study. Serum uric acid was found to exhibit significant heritability (0.42) in this population (P = 2 x 10^–7) after accounting for covariate effects. In addition, genetic correlations between serum uric acid and other cardiovascular risk factors, such as body mass index, waist circumference, systolic BP, and pulse pressure, were identified, suggesting that the genes associated with uric acid level are also associated with these phenotypes. Multipoint linkage analysis identified quantitative trait loci with measurable effects on serum uric acid variability. The highest multipoint logarithm of odds score of 3.3 was found at 133 cM on chromosome 6q22–23, a region that also contains genes that seem to influence familial IgA nephropathy, obesity, BP, insulin resistance, and type 2 diabetes. Given the relationship between uric acid level and these conditions, future studies should investigate potential candidate susceptibility genes found in this region.

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Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673