Abstract
Increased serum uric acid (SUA) or hyperuricemia, a risk factor for gout, renal and cardiovascular diseases, is caused by either increased production or decreased excretion of uric acid or a mix of both. The solute carrier protein 2 family, member 9 (SLC2A9) gene encodes a transporter that mediates urate flux across the renal proximal tubule. Genome-wide association studies have consistently shown the association of single-nucleotide polymorphisms in this gene with SUA in majority populations. American Indian participants of the Strong Heart Family Study, belonging to multigenerational families, have high prevalence of hyperuricemia. We conducted measured genotype analyses, based on variance components decomposition method and accounting for family relationships, to assess whether the association between SUA and SLC2A9 gene polymorphisms generalized to American Indians (n=3604) of this study. Seven polymorphisms were selected for genotyping based on their association with SUA levels in other populations. A strong association was found between SLC2A9 gene polymorphisms and SUA in all centers combined (P-values: 1.3 × 10−31–5.1 × 10−23) and also when stratified by recruitment center; P-values: 1.2 × 10−14–1.0 × 10−5. These polymorphisms were also associated with the estimated glomerular filtration rate and serum creatinine but not albumin–creatinine ratio. In summary, the association of polymorphisms in the uric acid transporter gene with SUA levels extends to a new population of American Indians.
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Acknowledgements
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 Population Architecture Using Genomics and Epidemiology (PAGE) program is funded by the National Human Genome Research Institute (NHGRI), supported by U01HG004803 (CALiCo), U01HG004798 (EAGLE), U01HG004802 (MEC), U01HG004790 (WHI) and U01HG004801 (Coordinating Center), and their respective NHGRI ARRA supplements. The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. The complete list of PAGE members can be found at http://www.pagestudy.org. This work was also supported by cooperative agreements HL65520, HL41642, HL41652, HL41654 and HL65521, and TR000101 and by NIDDK grant R01DK092238. 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 grants C06 RR013556 and C06 RR017515.
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Voruganti, V., Franceschini, N., Haack, K. et al. Replication of the effect of SLC2A9 genetic variation on serum uric acid levels in American Indians. Eur J Hum Genet 22, 938–943 (2014). https://doi.org/10.1038/ejhg.2013.264
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DOI: https://doi.org/10.1038/ejhg.2013.264
