title: Polymorphisms in the presumptive promoter region of the SLC2A9 gene are associated with gout in a Chinese male population.
abstract: BACKGROUND
  Glucose transporter 9 (GLUT9) is a high-capacity/low-affinity urate transporter. To date, several recent genome-wide association studies (GWAS) and follow-up studies have identified genetic variants of SLC2A9 associated with urate concentrations and susceptibility to gout. We therefore investigated associations between gout and polymorphisms and haplotypes in the presumptive promoter region of GLUT9 in Chinese males.
  
  
  RESULTS
  The approximately 2000 bp presumptive promoter region upstream of the start site of exon 1 of GLUT9 was sequenced and subjected to genetic analysis. A genotype-phenotype correlation was performed and polymorphisms-induced changes in transcription factor binding sites were predicted. Of 21 SNPs identified in GLUT9, five had not been previously reported. Two of the SNPs (rs13124007 and rs6850166) were associated with susceptibility to gout (p = 0.009 and p = 0.042, respectively). The C allele of rs13124007 appeared to be the risk allele for predisposition to gout (p = 0.006, OR 1.709 [95% CI 1.162-2.514]). For rs6850166, an increased risk of gout was associated with the A allele (p = 0.029, OR 1.645 [95% CI 1.050-2.577]). After Bonferroni correction, there was statistically difference in rs13124007 allele frequencies between gout cases and controls (P = 0.042). Haplotype analyses showed that haplotype GG was a protective haplotype (p = 0.0053) and haplotype CA was associated with increased risk of gout (p = 0.0326). Genotype-phenotype analysis among gout patients revealed an association of rs13124007 with serum triglycerides levels (P = 0.001). The C to G substitution in polymorphism rs13124007 resulted in a loss of a binding site for transcription factor interferon regulatory factor 1 (IRF-1).
  
  
  CONCLUSIONS
  Polymorphisms rs13124007 and rs6850166 are associated with susceptibility to gout in Chinese males.
authors.affiliation: The Affiliated Hospital of Medical College, Qingdao University, Qingdao, China. lichanggui@medmail.com.cn
authors.forename: Changgui
authors.initials: C
authors.lastname: Li
authors.forename: Nan
authors.initials: N
authors.lastname: Chu
authors.forename: Binbin
authors.initials: B
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Luan
authors.forename: Lin
authors.initials: L
authors.lastname: Han
authors.forename: Dongmei
authors.initials: D
authors.lastname: Meng
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Wang
authors.forename: Peisu
authors.initials: P
authors.lastname: Suo
authors.forename: Longfei
authors.initials: L
authors.lastname: Cheng
authors.forename: Xu
authors.initials: X
authors.lastname: Ma
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Miao
authors.forename: Shiguo
authors.initials: S
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D002681:China; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics*; D006073:Gout / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
chemical_list: D051246:Glucose Transport Proteins, Facilitative; C411811:SLC2A9 protein, human