title: Genome-wide association analysis confirms and extends the association of SLC2A9 with serum uric acid levels to Mexican Americans.
abstract: Increased serum uric acid (SUA) is a risk factor for gout and renal and cardiovascular disease (CVD). The purpose of this study was to identify genetic factors that affect the variation in SUA in 632 Mexican Americans participants of the San Antonio Family Heart Study (SAFHS). A genome-wide association (GWA) analysis was performed using the Illumina Human Hap 550K single nucleotide polymorphism (SNP) microarray. We used a linear regression-based association test under an additive model of allelic effect, while accounting for non-independence among family members via a kinship variance component. All analyses were performed in the software package SOLAR. SNPs rs6832439, rs13131257, and rs737267 in solute carrier protein 2 family, member 9 (SLC2A9) were associated with SUA at genome-wide significance (p < 1.3 × 10(-7)). The minor alleles of these SNPs had frequencies of 36.2, 36.2, and 38.2%, respectively, and were associated with decreasing SUA levels. All of these SNPs were located in introns 3-7 of SLC2A9, the location of the previously reported associations in European populations. When analyzed for association with cardiovascular-renal disease risk factors, conditional on SLC2A9 SNPs strongly associated with SUA, significant associations were found for SLC2A9 SNPs with BMI, body weight, and waist circumference (p < 1.4 × 10(-3)) and suggestive associations with albumin-creatinine ratio and total antioxidant status (TAS). The SLC2A9 gene encodes an urate transporter that has considerable influence on variation in SUA. In addition to the primary association locus, suggestive evidence (p < 1.9 × 10(-6)) for joint linkage/association (JLA) was found at a previously-reported urate quantitative trait locus (Logarithm of odds score = 3.6) on 3p26.3. In summary, our GWAS extends and confirms the association of SLC2A9 with SUA for the first time in a Mexican American cohort and also shows for the first time its association with cardiovascular-renal disease risk factors.
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute San Antonio, TX, USA ; Department of Nutrition, Nutrition Research Institute, University of North Carolina at Chapel Hill Kannapolis, NC, USA.
authors.forename: Venkata Saroja
authors.initials: VS
authors.lastname: Voruganti
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute San Antonio, TX, USA.
authors.forename: Jack W
authors.initials: JW
authors.lastname: Kent
authors.affiliation: Division of Nephrology, Department of Medicine, University of Texas Health Science Center at San Antonio San Antonio, TX, USA.
authors.forename: Subrata
authors.initials: S
authors.lastname: Debnath
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute San Antonio, TX, USA.
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Cole
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute San Antonio, TX, USA.
authors.forename: Karin
authors.initials: K
authors.lastname: Haack
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute San Antonio, TX, USA.
authors.forename: Harald H H
authors.initials: HH
authors.lastname: Göring
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute San Antonio, TX, USA.
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Carless
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute San Antonio, TX, USA.
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Curran
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute San Antonio, TX, USA.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Johnson
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute San Antonio, TX, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Almasy
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute San Antonio, TX, USA.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Dyer
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute San Antonio, TX, USA.
authors.forename: Jean W
authors.initials: JW
authors.lastname: Maccluer
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute San Antonio, TX, USA ; Centre for Genetic Origins of Health and Disease, University of Western Australia Perth, WA, Australia.
authors.forename: Eric K
authors.initials: EK
authors.lastname: Moses
authors.affiliation: Division of Nephrology, Department of Medicine, University of Texas Health Science Center at San Antonio San Antonio, TX, USA.
authors.forename: Hanna E
authors.initials: HE
authors.lastname: Abboud
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute San Antonio, TX, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Mahaney
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute San Antonio, TX, USA.
authors.forename: John
authors.initials: J
authors.lastname: Blangero
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute San Antonio, TX, USA.
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Comuzzie
keywords: hyperuricemia; joint linkage/association analysis; kinship; variance components decomposition approach