title: Discovery of URAT1 SNPs and association between serum uric acid levels and URAT1.
abstract: OBJECTIVE
  Human urate transporter 1 (URAT1) is a member of the organic anion transporter family (SLC22A12) that primarily regulates the renal tubular reabsorption of uric acid. This case-control study was designed to analyse whether hURAT1 might also be a candidate gene for hyperuricaemia or hypouricaemia.
  
  
  METHODS
  We recruited 68 healthy volunteers and divided them into two groups: a normal uric acid group and a hyperuricaemia group. We analysed the sequence of the URAT1 gene and found five significant single nucleotide polymorphisms (SNPs). We then selected 900 male subjects from the 262,200 enrolled in the Korean Cancer Prevention Study-II (KCPS-II) cohort for further genetic analysis.
  
  
  METHODS
  DNA samples from 36 individuals with normal uric acid (<4.5 mg/dL) and 32 individuals with hyperuricaemia (>8.5 mg/dL) were sequenced. Five significant SNPs (rs7929627, rs75786299, rs3825017, rs11602903 and rs121907892) were identified. We then chose 900 subjects from the KCPS-II cohort consisting of 450 subjects with normal uric acid (UA <4.1 mg/dL) and 450 subjects with hyperuricaemia (UA >8.7 mg/dL). The groups were matched by age, body mass index, metabolic syndrome and use of anti-hypertensive medication.
  
  
  METHODS
  We compared the OR of the incidence of hyperuricaemia by URAT1 genotype.
  
  
  RESULTS
  The strongest association with hyperuricaemia was observed for rs75786299 (IVS3+11A/G) with an OR of 32.05. rs7929627 (IVS7-103A/G) and rs3825017 (N82N) showed an association with hyperuricaemia with ORs of 2.56 and 2.29, respectively. rs11602903 (788A/T) and rs121907892 (W258X) were negatively correlated with hyperuricaemia with ORs of 0.350 and 0.447, respectively. Individuals carrying the GATAG haplotype (n=32)-a relatively common variant consisting of rs7929627, rs75786299 and rs3825017-showed the highest risk for hyperuricaemia with an OR of 92.23 (p=9.55×10(-3)).
  
  
  CONCLUSIONS
  These results indicate that five newly described SNPs in the hURAT1 gene are significantly associated with uric acid level (4-2008-0318 and 4-2011-0277).
authors.affiliation: Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sung Kweon
authors.initials: SK
authors.lastname: Cho
authors.affiliation: Department of Epidemiology and Health Promotion and Institute for Health Promotion, Graduate School of Public Health, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Soriul
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Bundang Hospital, Seongnam, Korea.
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Chung
authors.affiliation: Department of Epidemiology and Health Promotion and Institute for Health Promotion, Graduate School of Public Health, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sun Ha
authors.initials: SH
authors.lastname: Jee
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D033461:Hyperuricemia / Q000097:blood / Q000235:genetics*; D008297:Male; D009154:Mutation; D016017:Odds Ratio; D027361:Organic Anion Transporters / Q000235:genetics*; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea; D014527:Uric Acid / Q000097:blood*; D055815:Young Adult
chemical_list: D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; C491241:SLC22A12 protein, human; D014527:Uric Acid
keywords: CLINICAL PHARMACOLOGY; GENETICS