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Multiple single nucleotide polymorphisms in the human urate transporter 1 (hURAT1) gene are associated with hyperuricaemia in Han Chinese
  1. Changgui Li1,
  2. Lin Han1,
  3. Albert M Levin2,
  4. Huaidong Song3,
  5. Shengli Yan1,
  6. Yao Wang1,
  7. Yunlong Wang1,
  8. Dongmei Meng1,
  9. Sensen lv1,
  10. Yan Ji1,
  11. Xiaochen Xu1,
  12. Xianxian Liu1,
  13. Yangang Wang1,
  14. Li Zhou4,5,6,
  15. Zhimin Miao1,
  16. Qing-Sheng Mi4,5,6
  1. 1Gout laboratory, Medical School Hospital of Qingdao University, Qingdao, China
  2. 2Department of Biostatistics and Research Epidemiology, Henry Ford Health System, Detroit, Michigan, USA
  3. 3State Key Laboratory of Medical Genomics, Shanghai Institute of Endocrine and Metabolic Diseases, Center of Molecular Medicine, Ruijin Hospital, Shanghai Jiaotong University Medical School, Shanghai, China
  4. 4Henry Ford Immunology Program, Detroit, Michigan, USA
  5. 5Department of Dermatology, Detroit, Michigan, USA
  6. 6Department of Internal Medicine, Henry Ford Health System, Detroit, Michigan, USA
  1. Correspondence to Dr Qing-Sheng Mi, Henry Ford Immunology Program, Department of Dermatology and Department of Internal Medicine, Henry Ford Health System, 1 Ford Place, Detroit, MI 48202, United States. qmi1{at}hfhs.org; Dr Zhimin Miao, Gout Laboratory, Medical School Hospital of Qingdao University, 16 Jiangsu Road, Qingdao 266003, China; miaozhm{at}qdumh.qd.sd.cn

Abstract

Objective The present study investigated whether single nucleotide polymorphisms (SNPs) in the human urate transporter 1 (hURAT1) gene are associated with primary hyperuricaemia (HUA) in Han Chinese people.

Methods A total of 538 subjects (215 cases and 323 control subjects) were recruited from Qingdao, China. SNPs in potentially functional regions of the gene were identified and genotypes determined by direct sequencing. Association analyses were conducted using Fisher's exact test and logistic regression assuming a genotype model.

Results By sequencing the promoter, 10 exons, and the exon-intron junctions of the hURAT1 gene, 14 SNPs were identified. Two of the SNPs identified were associated with susceptibility to HUA. The first was a rare intron 3 (11 G→A) SNP (p=0.0005), where carriers of the ‘A’ allele had a 3.4-fold (95% CI 1.67 to 6.93) increased risk of HUA. The second was a common exon 8 (T1309C) SNP (rs7932775), where carriers of one and two ‘C’ alleles had respective fold increased risks of 1.64 (95% CI 1.07 to 2.52) and 2.32 (95% CI 1.37 to 3.95). These SNPs had a joint additive effect of risk of HUA, with those individuals carrying at least one ‘A’ allele at the intron 3 SNP and two ‘C’ alleles at rs7932775 having a 5.88-fold (95% CI 1.25 to 15.57) increased risk of HUA in comparison to those with no risk alleles.

Conclusion In conjunction with other studies, our results suggest that there are multiple genetic variants within or near hURAT1 that are associated with susceptibility to HUA in Han Chinese, including a novel SNP located in intron 3.

  • Hurat1
  • hyperuricaemia
  • single nucleotide polymorphisms (SNPs)
  • endocrinology
  • genetic screening
  • molecular genetics

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Footnotes

  • CL, LH and AML contributed equally to this work.

  • Funding Other Funders: National Science Foundation of China and Henry Ford Health System Research Fund.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Qingdao University.

  • Patient consent Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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