Replication of the effect of SLC2A9 genetic variation on serum uric acid levels in American Indians. 

 -  2014 
<br/><br/> 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 x 10(-31)-5.1 x 10(-23)) and also when stratified by recruitment center; P-values: 1.2 x 10(-14)-1.0 x 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. 
<br/><br/><br/>English 
<br/><br/><label>ISSN: </label>1018-4813 
<br/><br/><label>Subjects--Topical Terms: </label><br/>*Genetic Predisposition to Disease<br/>*Genome-Wide Association Study<br/>*Glucose Transport Proteins, Facilitative/ge [Genetics]<br/>*Hyperuricemia<br/>*Indians, North American/ge [Genetics]<br/>*Polymorphism, Genetic<br/>*Uric Acid/bl [Blood]<br/>Adult<br/>Female<br/>Genotype<br/>Glomerular Filtration Rate/ge [Genetics]<br/>Glucose Transport Proteins, Facilitative/me [Metabolism]<br/>Humans<br/>Hyperuricemia/bl [Blood]<br/>Hyperuricemia/ge [Genetics]<br/>Male<br/>Middle Aged
<br/><br/><label>Subjects--Geographic Terms: </label><br/>MedStar Health Research Institute
<br/><br/><label>Index Terms--Function: </label><br/>Clinical Trial<br/>Journal Article<br/>Multicenter Study<br/>Research Support, American Recovery and Reinvestment Act<br/>Research Support, N.I.H., Extramural