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Association between SLC2A9 (GLUT9) gene polymorphisms and gout susceptibility: an updated meta-analysis

  • Genes and Disease
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Abstract

The relationship between the SLC2A9 (solute carrier family 2, member 9) gene polymorphisms and gout was still inconsistent among the individual genetic association studies. Therefore, this present research was aimed to systematically evaluate the association between SLC2A9 gene polymorphisms and gout susceptibility. Relevant studies were enrolled by searching databases systematically. The pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the associations. The heterogeneity between each of the studies was calculated by using the Q statistic methods, and Begg’s funnel plot and Egger’s tests were performed to evaluate publication bias. A total of 13 studies investigated four single nucleotide polymorphisms (SNPs) in SLC2A9 were included. In this study, we found that the allele C of rs3733591 was higher in patients than in controls in both all-pooled population [C vs. T: OR (95 % CI) = 1.432 (1.213–1.691)] and Asians-pooled population [C vs. T: OR (95 % CI) = 1.583 (1.365–1.835)]. The allele frequency C of s6449213 was lower in the gout patients than in controls in both all-pooled population and Caucasians-pooled population. Additionally, the allele frequency T of rs16890979 and the allele frequency C of rs1014290 were lower in gout patients than in controls. This study demonstrated that the genetic susceptibility for gout is associated with the SLC2A9 gene polymorphisms. Four of them except for the rs3733591 are protective SNPs in Caucasians, and rs16890979 and rs1014290 are protective SNPs in both Caucasians and Asians, while rs3733591 may be susceptibility SNP in Asians.

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References

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

    Article  CAS  PubMed  Google Scholar 

  2. Annemans L, Spaepen E, Gaskin M, Bonnemaire M, Malier V et al (2008) Gout in the UK and Germany: prevalence, comorbidities and management in general practice 2000-2005. Ann Rheum Dis 67(7):960–966

    Article  CAS  PubMed  Google Scholar 

  3. Zhu Y, Pandya BJ, Choi HK (2011) Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007–2008. Arthritis Rheum 63(10):3136–3141

    Article  PubMed  Google Scholar 

  4. Winnard D, Wright C, Taylor WJ, Jackson G et al (2012) National prevalence of gout derived from administrative health data in Aotearoa New Zealand. Rheumatology (Oxford) 51(5):901–909

    Article  Google Scholar 

  5. Schlesinger N, Thiele RG (2010) The pathogenesis of bone erosions in gouty arthritis. Ann Rheum Dis 69(11):1907–1912

    Article  CAS  PubMed  Google Scholar 

  6. Perez-Ruiz F, Castillo E, Chinchilla SP, Herrero-Beites AM (2014) Clinical manifestations and diagnosis of gout. Rheum Dis Clin North Am 40(2):193–206

    Article  PubMed  Google Scholar 

  7. Roddy E, Mallen CD, Doherty M (2013) Gout. BMJ (Clinical Research ed) 347:f5648

    Google Scholar 

  8. Ning TC, Keenan RT (2010) Unusual clinical presentations of gout. Curr Opin Rheumatol 22(2):181–187

    Article  PubMed  Google Scholar 

  9. Roddy E, Choi HK (2014) Epidemiology of gout. Rheum Dis Clin North Am 40(2):155–175

    Article  PubMed  PubMed Central  Google Scholar 

  10. Smith E, Hoy D, Cross M, Merriman TR et al (2014) The global burden of gout: estimates from the Global Burden of Disease 2010 study. Ann Rheum Dis 73(8):1470–1476

    Article  PubMed  Google Scholar 

  11. Arromdee E, Michet CJ, Crowson CS, O’Fallon WM, Gabriel SE (2002) Epidemiology of gout: Is the incidence rising? J Rheumatol 29(11):2403–2406

    PubMed  Google Scholar 

  12. Mikuls TR, Saag KG (2006) New insights into gout epidemiology. Curr Opin Rheumatol 18(2):199–203

    Article  PubMed  Google Scholar 

  13. Choi HK, Atkinson K, Karlson EW, Curhan G (2005) Obesity, weight change, hypertension, diuretic use, and risk of gout in men: the health professionals follow-up study. Arch Intern Med 165(7):742–748

    Article  PubMed  Google Scholar 

  14. Edwards NL (2008) The role of hyperuricemia and gout in kidney and cardiovascular disease. Clevel Clin J Med 75(Suppl 5):S13–S16

    Article  Google Scholar 

  15. Bhole V, de Vera M, Rahman MM, Krishnan E, Choi H (2010) Epidemiology of gout in women: fifty-two-year followup of a prospective cohort. Arthritis Rheum 62(4):1069–1076

    Article  PubMed  Google Scholar 

  16. Hueskes BA, Roovers EA, Mantel-Teeuwisse AK, Janssens HJ et al (2012) Use of diuretics and the risk of gouty arthritis: a systematic review. Semin Arthritis Rheum 41(6):879–889

    Article  CAS  PubMed  Google Scholar 

  17. Choi HK, Curhan G (2005) Gout: epidemiology and lifestyle choices. Curr Opin Rheumatol 17(3):341–345

    PubMed  Google Scholar 

  18. Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G (2004) Alcohol intake and risk of incident gout in men: a prospective study. Lancet (London, England) 363(9417):1277–1281

    Article  Google Scholar 

  19. Reginato AM, Mount DB, Yang I, Choi HK (2012) The genetics of hyperuricaemia and gout. Nat Rev Rheumatol 8(10):610–621

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Merriman TR, Choi HK, Dalbeth N (2014) The genetic basis of gout. Rheum Dis Clin North Am 40(2):279–290

    Article  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  22. Urano W, Taniguchi A, Anzai N, Inoue E et al (2010) Sodium-dependent phosphate cotransporter type 1 sequence polymorphisms in male patients with gout. Ann Rheum Dis 69(6):1232–1234

    Article  CAS  PubMed  Google Scholar 

  23. Li S, Sanna S, Maschio A, Busonero F, Usala G et al (2007) The GLUT9 gene is associated with serum uric acid levels in Sardinia and Chianti cohorts. PLoS Genet 3(11):e194

    Article  PubMed  PubMed Central  Google Scholar 

  24. Augustin R, Carayannopoulos MO, Dowd LO, Phay JE, Moley JF, Moley KH (2004) Identification and characterization of human glucose transporter-like protein-9 (GLUT9): alternative splicing alters trafficking. J Biol Chem 279(16):16229–16236

    Article  CAS  PubMed  Google Scholar 

  25. Doring A, Gieger C, Mehta D, Gohlke H et al (2008) SLC2A9 influences uric acid concentrations with pronounced sex-specific effects. Nat Genet 40(4):430–436

    Article  PubMed  Google Scholar 

  26. Vitart V, Rudan I, Hayward C, Gray NK et al (2008) SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout. Nat Genet 40(4):437–442

    Article  CAS  PubMed  Google Scholar 

  27. Brandstatter A, Kiechl S, Kollerits B, Hunt SC et al (2008) Sex-specific association of the putative fructose transporter SLC2A9 variants with uric acid levels is modified by BMI. Diabetes Care 31(8):1662–1667

    Article  PubMed  PubMed Central  Google Scholar 

  28. Meng Q, Yue J, Shang M, Shan Q, Qi J, Mao Z, Li J, Zhang F, Wang B, Zhao T, Wang W (2015) Correlation of GLUT9 Polymorphisms With Gout Risk. Medicine (Baltimore) 94(44):e1742

    Article  CAS  Google Scholar 

  29. Stark K, Reinhard W, Neureuther K, Wiedmann S, Sedlacek K, Baessler A, Fischer M, Weber S, Kaess B, Erdmann J, Schunkert H, Hengstenberg C (2008) Association of common polymorphisms in GLUT9 gene with gout but not with coronary artery disease in a large case-control study. PLoS One 3(4):e1948. doi:10.1371/journal.pone.0001948

    Article  PubMed  PubMed Central  Google Scholar 

  30. Hollis-Moffatt JE, Gow PJ, Harrison AA, Highton J et al (2011) The SLC2A9 nonsynonymous Arg265His variant and gout: evidence for a population-specific effect on severity. Arthritis Res Ther 13(3):R85

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Wan W, Xu X, Zhao DB, Pang YF, Wang YX (2015) Polymorphisms of uric transporter proteins in the pathogenesis of gout in a Chinese Han population. Genet Mol Res 14(1):2546–2550

    Article  CAS  PubMed  Google Scholar 

  32. Kim YS, Kim Y, Park G, Kim SK, Choe JY, Park BL, Kim HS (2015) Genetic analysis of ABCG2 and SLC2A9 gene polymorphisms in gouty arthritis in a Korean population. Korean J Intern Med 30(6):913–920

    Article  PubMed  PubMed Central  Google Scholar 

  33. Zhu ZH, Jin XZ, Zhang W, Chen M, Ye DQ et al (2014) Associations between vitamin D receptor gene polymorphisms and osteoarthritis: an updated meta-analysis. Rheumatol (Oxford) 53(6):998–1008

    Article  CAS  Google Scholar 

  34. Liu L, Fan D, Ding N, Hu Y, Cai G, Wang L, Xin L, Xia Q, Li X, Xu S, Xu J, Yang X, Zou Y, Pan F (2014) The relationship between DRD2 gene polymorphisms (C957T and C939T) and schizophrenia: a meta-analysis. Neurosci Lett 583:43–48

    Article  CAS  PubMed  Google Scholar 

  35. Hollis-Moffatt JE, Xu X, Dalbeth N, Merriman ME et al (2009) Role of the urate transporter SLC2A9 gene in susceptibility to gout in New Zealand Maori, Pacific Island, and Caucasian case-control sample sets. Arthritis Rheum 60(11):3485–3492

    Article  PubMed  Google Scholar 

  36. Urano W, Taniguchi A, Anzai N, Inoue E, Sekita C, Endou H, Kamatani N, Yamanaka H (2010) Association between GLUT9 and gout in Japanese men. Ann Rheum Dis 69(5):932–933

    Article  PubMed  Google Scholar 

  37. Tu HP, Chen CJ, Tovosia S, Ko AM, Lee CH et al (2010) Associations of a non-synonymous variant in SLC2A9 with gouty arthritis and uric acid levels in Han Chinese subjects and Solomon Islanders. Ann Rheum Dis 69(5):887–890

    Article  CAS  PubMed  Google Scholar 

  38. You Y, Yu Q, Xu C, Yang H, Li Y (2013) Association of single nucleotide polymorphisms of SLC2A9, SLC17A3 and ABCG2 gene with gout susceptibility in Quanzhou residents. Chin J Rheumatol 17(2):114–118

    CAS  Google Scholar 

  39. Torres RJ, de Miguel E, Bailen R, Banegas JR, Puig JG (2014) Tubular urate transporter gene polymorphisms differentiate patients with gout who have normal and decreased urinary uric acid excretion. J Rheumatol 41(9):1863–1870

    Article  CAS  PubMed  Google Scholar 

  40. Guo M, Wang Y, Qiu W, Li S, Cheng Z (2014) Research on the correlation of SLC2A9 rs1014290 polymorphism with gout in Northern Chinese Han male population. Prog Mod Biomed 36:7034–7036

    Google Scholar 

  41. Li M, Yang J, Zhou J, Qing Y, Xie W, Yang Q, Zhao M, Jiang D (2014) Association of the rs3733591 (C > T) polymorphism of SLC2A9 gene with primary gout in Chinese Han population. Chin J Rheumatol 18:655–660

    CAS  Google Scholar 

  42. McArdle PF, Parsa A, Chang YP, Weir MR, O’Connell JR, Mitchell BD, Shuldiner AR (2008) Association of a common nonsynonymous variant in GLUT9 with serum uric acid levels in old order amish. Arthritis Rheum 58(9):2874–2881

    Article  PubMed  PubMed Central  Google Scholar 

  43. Polasek O, Gunjaca G, Kolcic I, Zgaga L, Dzijan S, Smolic R, Smolic M, Milas-Ahic J, Seric V, Galic J, Tucak-Zoric S, Tucak A, Rudan I, Lauc G (2010) Association of nephrolithiasis and gene for glucose transporter type 9 (SLC2A9): study of 145 patients. Croat Med J 51(1):48–53

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. 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

    Article  PubMed  PubMed Central  Google Scholar 

  45. Yang B, Mo Z, Wu C, Yang H, Yang X, He Y, Gui L et al (2014) A genome-wide association study identifies common variants influencing serum uric acid concentrations in a Chinese population. BMC Med Genom 7:10

    Article  Google Scholar 

  46. Matsuo H, Yamamoto K, Nakaoka H, Nakayama A, Sakiyama M et al (2015) Genome-wide association study of clinically defined gout identifies multiple risk loci and its association with clinical subtypes. Ann Rheum Dis. doi:10.1136/annrheumdis-2014-206191

    PubMed  PubMed Central  Google Scholar 

  47. Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J (2006) Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440(7081):237–241

    Article  CAS  PubMed  Google Scholar 

  48. MacFarlane LA, Kim SC (2014) Gout: a review of nonmodifiable and modifiable risk factors. Rheum Dis Clin North Am 40(4):581–604

    Article  PubMed  PubMed Central  Google Scholar 

  49. Cronstein BN, Sunkureddi P (2013) Mechanistic aspects of inflammation and clinical management of inflammation in acute gouty arthritis. J Clin Rheumatol Pract Rep Rheum Musculoskelet Dis 19(1):19–29

    Google Scholar 

  50. Li M (2009) Association of the polymorphisms of SLC2A9 gene with primary gout and uric acid levels in Chinese Han population. Dissertation, North Sichuan Medical College

  51. Mobasheri A, Neama G, Bell S, Richardson S, Carter SD (2002) Human articular chondrocytes express three facilitative glucose transporter isoforms: GLUT1, GLUT3 and GLUT9. Cell Biol Int 26(3):297–300

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank all the individuals who have helped us in this study.

Funding

The study was supported by grants from the National Natural Science Foundation of China (30771849, 30972530, 81273169 and 81573218).

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    Authors and Affiliations

    1. Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, China

      Xu Zhang, Xiao Yang, Mengmeng Wang, Xiaona Li, Qing Xia, Guoqi Cai, Li Wang, Lihong Xin, Yanfeng Zou & Faming Pan

    2. Department of Rheumatism and Immunity, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, China

      Shengqian Xu & Jianhua Xu

    3. Arthritis Research Institute, 1st Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China

      Shengqian Xu, Jianhua Xu & Faming Pan

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    1. Xu Zhang
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    Correspondence to Faming Pan.

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    All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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    Xu Zhang and Xiao Yang have contributed equally to this work and should be considered co-first authors.

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    Zhang, X., Yang, X., Wang, M. et al. Association between SLC2A9 (GLUT9) gene polymorphisms and gout susceptibility: an updated meta-analysis. Rheumatol Int 36, 1157–1165 (2016). https://doi.org/10.1007/s00296-016-3503-6

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