Replication of the Effect of SLC2A9 Genetic Variation on Serum Uric Acid Levels in American Indians

Eur J Hum Genet. 2014 Jul;22(7):938-43. doi: 10.1038/ejhg.2013.264. Epub 2013 Dec 4.

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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Female
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study*
  • Genotype
  • Glomerular Filtration Rate / genetics
  • Glucose Transport Proteins, Facilitative / genetics*
  • Glucose Transport Proteins, Facilitative / metabolism
  • Humans
  • Hyperuricemia* / blood
  • Hyperuricemia* / genetics
  • Indians, North American / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Uric Acid / blood*

Substances

  • Glucose Transport Proteins, Facilitative
  • SLC2A9 protein, human
  • Uric Acid