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GWAS and transcriptional analysis prioritize ITPR1 and CNTN4 for a serum uric acid 3p26 QTL in Mexican Americans.
Chittoor, Geetha; Kent, Jack W; Almeida, Marcio; Puppala, Sobha; Farook, Vidya S; Cole, Shelley A; Haack, Karin; Göring, Harald H H; MacCluer, Jean W; Curran, Joanne E; Carless, Melanie A; Johnson, Matthew P; Moses, Eric K; Almasy, Laura; Mahaney, Michael C; Lehman, Donna M; Duggirala, Ravindranath; Comuzzie, Anthony G; Blangero, John; Voruganti, Venkata Saroja.
Affiliation
  • Chittoor G; Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Kent JW; UNC Nutrition Research Institute, University of North Carolina at Chapel Hill, 500 Laureate Way, Kannapolis, NC, 28081, USA.
  • Almeida M; Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
  • Puppala S; South Texas Diabetes and Obesity Institute, School of Medicine, University of Texas Rio Grande Valley, Brownsville, TX, USA.
  • Farook VS; Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
  • Cole SA; South Texas Diabetes and Obesity Institute, School of Medicine, University of Texas Rio Grande Valley, Brownsville, TX, USA.
  • Haack K; Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
  • Göring HH; Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
  • MacCluer JW; South Texas Diabetes and Obesity Institute, School of Medicine, University of Texas Rio Grande Valley, Brownsville, TX, USA.
  • Curran JE; Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
  • Carless MA; South Texas Diabetes and Obesity Institute, School of Medicine, University of Texas Rio Grande Valley, Brownsville, TX, USA.
  • Johnson MP; Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
  • Moses EK; South Texas Diabetes and Obesity Institute, School of Medicine, University of Texas Rio Grande Valley, Brownsville, TX, USA.
  • Almasy L; Centre for Genetic Epidemiology and Biostatistics, The University of Western Australia, Perth, WA, Australia.
  • Mahaney MC; South Texas Diabetes and Obesity Institute, School of Medicine, University of Texas Rio Grande Valley, Brownsville, TX, USA.
  • Lehman DM; South Texas Diabetes and Obesity Institute, School of Medicine, University of Texas Rio Grande Valley, Brownsville, TX, USA.
  • Duggirala R; Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
  • Comuzzie AG; South Texas Diabetes and Obesity Institute, School of Medicine, University of Texas Rio Grande Valley, Brownsville, TX, USA.
  • Blangero J; Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
  • Voruganti VS; South Texas Diabetes and Obesity Institute, School of Medicine, University of Texas Rio Grande Valley, Brownsville, TX, USA.
BMC Genomics ; 17: 276, 2016 Apr 02.
Article in En | MEDLINE | ID: mdl-27039371
ABSTRACT

BACKGROUND:

The variation in serum uric acid concentrations is under significant genetic influence. Elevated SUA concentrations have been linked to increased risk for gout, kidney stones, chronic kidney disease, and cardiovascular disease whereas reduced serum uric acid concentrations have been linked to multiple sclerosis, Parkinson's disease and Alzheimer's disease. Previously, we identified a novel locus on chromosome 3p26 affecting serum uric acid concentrations in Mexican Americans from San Antonio Family Heart Study. As a follow up, we examined genome-wide single nucleotide polymorphism data in an extended cohort of 1281 Mexican Americans from multigenerational families of the San Antonio Family Heart Study and the San Antonio Family Diabetes/Gallbladder Study. We used a linear regression-based joint linkage/association test under an additive model of allelic effect, while accounting for non-independence among family members via a kinship variance component.

RESULTS:

Univariate genetic analysis indicated serum uric acid concentrations to be significant heritable (h (2) = 0.50 ± 0.05, p < 4 × 10(-35)), and linkage analysis of serum uric acid concentrations confirmed our previous finding of a novel locus on 3p26 (LOD = 4.9, p < 1 × 10(-5)) in the extended sample. Additionally, we observed strong association of serum uric acid concentrations with variants in following candidate genes in the 3p26 region; inositol 1,4,5-trisphosphate receptor, type 1 (ITPR1), contactin 4 (CNTN4), decapping mRNA 1A (DCP1A); transglutaminase 4 (TGM4) and rho guanine nucleotide exchange factor (GEF) 26 (ARHGEF26) [p < 3 × 10(-7); minor allele frequencies ranged between 0.003 and 0.42] and evidence of cis-regulation for ITPR1 transcripts.

CONCLUSION:

Our results confirm the importance of the chromosome 3p26 locus and genetic variants in this region in the regulation of serum uric acid concentrations.
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Full text: 1 Database: MEDLINE Main subject: Uric Acid / Mexican Americans / Quantitative Trait Loci / Inositol 1,4,5-Trisphosphate Receptors / Contactins Type of study: Prognostic_studies Limits: Adult / Female / Humans / Male / Middle aged Country/Region as subject: Mexico Language: En Journal: BMC Genomics Journal subject: GENETICA Year: 2016 Type: Article Affiliation country: United States
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Full text: 1 Database: MEDLINE Main subject: Uric Acid / Mexican Americans / Quantitative Trait Loci / Inositol 1,4,5-Trisphosphate Receptors / Contactins Type of study: Prognostic_studies Limits: Adult / Female / Humans / Male / Middle aged Country/Region as subject: Mexico Language: En Journal: BMC Genomics Journal subject: GENETICA Year: 2016 Type: Article Affiliation country: United States