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Genetic variation in the ABCG2 gene is associated with gout risk in the Chinese Han population

Clinical Rheumatology volume 35, pages 159–163 (2016)Cite this article

Abstract

Gout is a common type of arthritis that is characterized by hyperuricemia, tophi, and joint inflammation. Current evidence suggests that heredity contributes to the progression of gout. Previous studies have shown that regulation of the ATP-binding cassette subfamily G member 2 (ABCG2) pathways plays a role in gout occurrence. To investigate and validate potential genetic associations with the risk of gout, we conducted a case–control study. We conducted 143 cases and 310 controls and genotyped seven single-nucleotide polymorphisms (SNPs) in ABCG2 gene. ABCG2 SNP association analyses were performed using SPSS 17.0 Statistical Package, PLINK Software, HaploView software package, and SHEsis software platform. We identified that four susceptibility SNPs were potentially associated with occurrence of gout. Rs2622621 and rs3114018 in ABCG2 can actually increase the risk of gout in log-additive model (rs2622621, odds ratio (OR) = 1.90, 95 % confidence interval (CI) 1.39–2.61, p < 0.001; rs3114018, OR = 1.55, 95 % CI 1.13–2.13, p = 0.006). We found that rs17731799G/T-G/G and rs3114020 T/C-T/T in ABCG2 can actually increase the risk of gout in dominant model (rs17731799, OR = 1.67, 95 % CI 1.05–2.66, p = 0.028; rs3114020, OR = 1.58, 95 % CI 1.00–2.51, p = 0.048). The ABCG2 haplotype “GGCTCTC” (OR = 0.46, 95 % CI 0.28–0.75, p = 0.0019) decreased the gout risk. Our results, combined with those from previous studies, suggest that genetic variation in ABCG2 may influence gout susceptibility in the Han population.

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References

  1. Miao Z, Li C, Chen Y, Zhao S, Wang Y, Wang Z et al (2008) Dietary and lifestyle changes associated with high prevalence of hyperuricemia and gout in the Shandong coastal cities of Eastern China. J Rheumatol 35(9):1859–1864

    PubMed  Google Scholar 

  2. Choi HK, Mount DB, Reginato AM (2005) Pathogenesis of gout. Ann Intern Med 143(7):499–516

    PubMed  CAS  Article  Google Scholar 

  3. Zhang W, Doherty M, Pascual E, Bardin T, Barskova V, Conaghan P et al (2006) EULAR evidence based recommendations for gout. Part I: diagnosis. Report of a task force of the Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 65(10):1301–1311

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  4. Wang B, Miao Z, Liu S, Wang J, Zhou S, Han L et al (2010) Genetic analysis of ABCG2 gene C421A polymorphism with gout disease in Chinese Han male population. Hum Genet 127(2):245–246

    PubMed  Article  Google Scholar 

  5. Choi HK, Ford ES, Li C, Curhan G (2007) Prevalence of the metabolic syndrome in patients with gout: the Third National Health and Nutrition Examination Survey. Arthritis Rheum 57(1):109–115

    PubMed  Article  Google Scholar 

  6. Choi HK, De Vera MA, Krishnan E (2008) Gout and the risk of type 2 diabetes among men with a high cardiovascular risk profile. Rheumatology (Oxford, England) 47(10):1567–1570

    CAS  Article  Google Scholar 

  7. Basseville A, Bates SE (2011) Gout, genetics and ABC transporters. F1000 Biol Rep 3:23

    PubMed  PubMed Central  Article  Google Scholar 

  8. Dehghan A, Kottgen A, Yang Q, Hwang SJ, Kao WL, Rivadeneira F et al (2008) Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study. Lancet 372(9654):1953–1961

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  9. Woodward OM, Kottgen A, Coresh J, Boerwinkle E, Guggino WB, Kottgen M (2009) Identification of a urate transporter, ABCG2, with a common functional polymorphism causing gout. Proc Natl Acad Sci U S A 106(25):10338–10342

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  10. Ichida K, Matsuo H, Takada T, Nakayama A, Murakami K, Shimizu T et al (2012) Decreased extra-renal urate excretion is a common cause of hyperuricemia. Nat Commun 3:764

    PubMed  PubMed Central  Article  Google Scholar 

  11. Gabriel S, Ziaugra L, Tabbaa D (2009) SNP genotyping using the Sequenom MassARRAY iPLEX platform. Curr Protoc Hum Genet 2.12. 1–2.. 6

  12. Thomas RK, Baker AC, Debiasi RM, Winckler W, Laframboise T, Lin WM et al (2007) High-throughput oncogene mutation profiling in human cancer. Nat Genet 39(3):347–351

    PubMed  CAS  Article  Google Scholar 

  13. Adamec C (1964) Example of the use of the nonparametric test. Test X2 for comparison of 2 independent examples. Ceskoslovenske zdravotnictvi 12:613–619

    PubMed  CAS  Google Scholar 

  14. Bland JM, Altman DG (2000) Statistics notes. The odds ratio. BMJ 320(7247):1468

    PubMed  CAS  PubMed Central  Article  Google Scholar 

  15. Sole X, Guino E, Valls J, Iniesta R, Moreno V (2006) SNPStats: a web tool for the analysis of association studies. Bioinformatics (Oxford, England) 22(15):1928–1929

    CAS  Article  Google Scholar 

  16. Wu EQ, Patel PA, Yu AP, Mody RR, Cahill KE, Tang J et al (2008) Disease-related and all-cause health care costs of elderly patients with gout. J Manag Care Pharm 14(2):164–175

    PubMed  Google Scholar 

  17. Kolz M, Johnson T, Sanna S, Teumer A, Vitart V, Perola M et al (2009) Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations. PLoS Genet 5(6), e1000504

    PubMed  PubMed Central  Article  Google Scholar 

  18. Stark K, Reinhard W, Grassl M, Erdmann J, Schunkert H, Illig T et al (2009) Common polymorphisms influencing serum uric acid levels contribute to susceptibility to gout, but not to coronary artery disease. PLoS One 4(11), e7729

    PubMed  PubMed Central  Article  Google Scholar 

  19. Matsuo H, Takada T, Ichida K, Nakamura T, Nakayama A, Ikebuchi Y et al (2009) Common defects of ABCG2, a high-capacity urate exporter, cause gout: a function-based genetic analysis in a Japanese population. Sci Transl Med 1(5):5ra11

    PubMed  Article  Google Scholar 

  20. Maliepaard M, Scheffer GL, Faneyte IF, van Gastelen MA, Pijnenborg AC, Schinkel AH et al (2001) Subcellular localization and distribution of the breast cancer resistance protein transporter in normal human tissues. Cancer Res 61(8):3458–3464

    PubMed  CAS  Google Scholar 

  21. Huls M, Brown CD, Windass AS, Sayer R, van den Heuvel JJ, Heemskerk S et al (2008) The breast cancer resistance protein transporter ABCG2 is expressed in the human kidney proximal tubule apical membrane. Kidney Int 73(2):220–225

    PubMed  CAS  Article  Google Scholar 

  22. Matsuo H, Ichida K, Takada T, Nakayama A, Nakashima H, Nakamura T et al (2013) Common dysfunctional variants in ABCG2 are a major cause of early-onset gout. Sci Rep 3:2014

    PubMed  PubMed Central  Article  Google Scholar 

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Acknowledgments

This work is supported by the National Natural Science Foundation of China (No. 31260252), Natural Science Foundation of Xizang (Tibet) Autonomous Region (20152R-13-11), and the Social Science Foundation of Chinese Ministry of Education (No. 12YJA850011). We are grateful to all the patients and individuals in the study who made this work possible. We would also like to thank the clinicians and hospital staff who contributed to data collection for this study.

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Affiliations

  1. Key Laboratory for Basic Life Science Research of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, #6 East Wenhui Road, Xianyang, 712082, Shaanxi, China

    Mutu Jiri, Bing Lan, Na He, Tianbo Jin & Longli Kang

  2. Key Laboratory for Molecular Genetic Mechanisms and Intervention Research on High Altitude Disease of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, 712082, China

    Mutu Jiri, Bing Lan, Na He, Tianbo Jin & Longli Kang

  3. School of Life Sciences, Northwest University, Mailbox 386, #229 North Taibai Road, Xi’an, 710069, Shaanxi, China

    Le Zhang & Tianbo Jin

  4. National Engineering Research Center for Miniaturized Detection Systems, Xi’an, Shaanxi, 710069, China

    Le Zhang, Tian Feng & Tianbo Jin

  5. Tibet Vocational Technical College, Tibet Autonomous Region, Lasa, 850000, China

    Kai Liu

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  1. Mutu Jiri
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  2. Le Zhang
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  3. Bing Lan
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  4. Na He
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  5. Tian Feng
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  6. Kai Liu
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  7. Tianbo Jin
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Correspondence to Tianbo Jin or Longli Kang.

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Mutu Jiri and Le Zhang joint first author.

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Jiri, M., Zhang, L., Lan, B. et al. Genetic variation in the ABCG2 gene is associated with gout risk in the Chinese Han population. Clin Rheumatol 35, 159–163 (2016). https://doi.org/10.1007/s10067-015-3105-9

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  • DOI: https://doi.org/10.1007/s10067-015-3105-9

Keywords

  • ABCG2
  • Case–control studies
  • Gout
  • Single-nucleotide polymorphism