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Genetic influence on variation in serum uric acid in American Indians: the strong heart family study

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Abstract

Hyperuricemia is associated with the metabolic syndrome, gout, renal and cardiovascular disease (CVD). American Indians have high rates of CVD and 25% of individuals in the strong heart family study (SHFS) have high serum uric acid levels. The aim of this study was to investigate the genetic determinants of serum uric acid variation in American Indian participants of the SHFS. A variance component decomposition approach (implemented in SOLAR) was used to conduct univariate genetic analyses in each of three study centers and the combined sample. Serum uric acid was adjusted for age, sex, age × sex, BMI, estimated glomerular filtration rate, alcohol intake, diabetic status and medications. Overall mean ± SD serum uric acid for all individuals was 5.14 ± 1.5 mg/dl. Serum uric acid was found to be significantly heritable (0.46 ± 0.03 in all centers, and 0.39 ± 0.07, 0.51 ± 0.05, 0.44 ± 0.06 in Arizona, Dakotas and Oklahoma, respectively). Multipoint linkage analysis showed significant evidence of linkage for serum uric acid on chromosome 11 in the Dakotas center [logarithm of odds score (LOD) = 3.02] and in the combined sample (LOD = 3.56) and on chromosome 1 (LOD = 3.51) in the combined sample. A strong positional candidate gene in the chromosome 11 region is solute carrier family22, member 12 (SLC22A12) that encodes a major uric acid transporter URAT1. These results show a significant genetic influence and a possible role for one or more genes on chromosomes 1 and 11 on the variation in serum uric acid in American Indian populations.

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Acknowledgments

We thank the SHFS participants, Indian Health Services facilities, and participating tribal communities for their extraordinary cooperation and involvement, and without whose assistance, this project would not have been possible. The opinions expressed in this paper are those of the author(s) and do not necessarily reflect the views of the Indian Health Service. This work was also supported by grants U01-HL65520, U01-HL41642, U01-HL41652, U01-HL41654 and U01-HL65521 from the National Heart, Lung, and Blood Institute, Bethesda, MD. Development of SOLAR was supported by NIH grant MH59490. This investigation was conducted in part in facilities constructed with support from the Research Facilities Improvement Program under grant numbered C06 RR014578, C06 RR013556, C06 RR015456, and C06 RR017515.

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  1. Department of Genetics, Southwest Foundation for Biomedical Research, P.O. Box 760549, San Antonio, TX, 78245-0549, USA

    V. Saroja Voruganti, Harald H. H. Göring, Karin Haack, Sandra Laston, Laura Almasy, Jean W. MacCluer, Anthony G. Comuzzie & Shelley A. Cole

  2. UNC Kidney Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Amy Mottl

  3. Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Nora Franceschini

  4. The National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA

    Richard R. Fabsitz

  5. University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    Elisa T. Lee

  6. Missouri Breaks Industries Research Inc, Timber Lake, SD, USA

    Lyle G. Best

  7. New York Presbyterian Hospital, Weill Medical College of Cornell University, New York, NY, USA

    Richard B. Devereux

  8. Medstar Research Institute, Washington, DC, USA

    Barbara V. Howard & Jason G. Umans

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  1. V. Saroja Voruganti
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Correspondence to V. Saroja Voruganti.

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Voruganti, V.S., Göring, H.H.H., Mottl, A. et al. Genetic influence on variation in serum uric acid in American Indians: the strong heart family study. Hum Genet 126, 667–676 (2009). https://doi.org/10.1007/s00439-009-0716-8

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