title: Association analysis of the beta-3 adrenergic receptor Trp64Arg (rs4994) polymorphism with urate and gout.
abstract: The Arg64 allele of variant rs4994 (Trp64Arg) in the β3-adrenergic receptor gene has been associated with increased serum urate and risk of gout. Our objective was to investigate the relationship of rs4994 with serum urate and gout in New Zealand European, Māori and Pacific subjects. A total of 1730 clinically ascertained gout cases and 2145 controls were genotyped for rs4994 by Taqman(®). Māori and Pacific subjects were subdivided into Eastern Polynesian (EP) and Western Polynesian (WP) sample sets. Publicly available genotype data from the Atherosclerosis Risk in Communities Study and the Framingham Heart Study were utilized for serum urate association analysis. Multivariate logistic and linear regression adjusted for potential confounders was carried out using R version 2.15.2. No significant association of the minor Arg64 (G) allele of rs4994 with gout was found in the combined Polynesian cohorts (OR = 0.98, P = 0.88), although there was evidence, after adjustment for renal disease, for association in both the WP (OR = 0.53, P = 0.03) and the lower Polynesian ancestry EP sample sets (OR = 1.86, P = 0.05). There was no evidence for association with gout in the European sample set (OR = 1.11, P = 0.57). However, the Arg64 allele was positively associated with urate in the WP data set (β = 0.036, P = 0.004, P Corrected = 0.032). Association of the Arg64 variant with increased urate in the WP sample set was consistent with the previous literature, although the protective effect of this variant with gout in WP was inconsistent. This association provides an etiological link between metabolic syndrome components and urate homeostasis.
authors.affiliation: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors.forename: Tahzeeb
authors.initials: T
authors.lastname: Fatima
authors.affiliation: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors.forename: Sara
authors.initials: S
authors.lastname: Altaf
authors.affiliation: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors.forename: Amanda
authors.initials: A
authors.lastname: Phipps-Green
authors.affiliation: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors.forename: Ruth
authors.initials: R
authors.lastname: Topless
authors.affiliation: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors.forename: Tanya J
authors.initials: TJ
authors.lastname: Flynn
authors.affiliation: Department of Medicine, University of Otago, Christchurch, New Zealand.
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Stamp
authors.affiliation: Department of Medicine, University of Auckland, Auckland, New Zealand.
authors.forename: Nicola
authors.initials: N
authors.lastname: Dalbeth
authors.affiliation: Department of Biochemistry, University of Otago, Dunedin, New Zealand. tony.merriman@otago.ac.nz.
authors.forename: Tony R
authors.initials: TR
authors.lastname: Merriman
mesh_terms: D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006073:Gout / Q000097:blood / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D033461:Hyperuricemia / Q000097:blood / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D016014:Linear Models; D016015:Logistic Models; D015999:Multivariate Analysis; D009520:New Zealand / Q000453:epidemiology; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D011114:Polynesia / Q000453:epidemiology; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics*; D012307:Risk Factors; D014527:Uric Acid / Q000097:blood*; D044465:White People / Q000235:genetics
chemical_list: C568534:ADRB3 protein, human; D015415:Biomarkers; D022702:Receptors, Adrenergic, beta-3; D014527:Uric Acid
keywords: ADRB3; Association; Genetic; Gout; Urate