Current Rheumatology Reports

, 15:309 | Cite as

Genetics of Hyperuricemia and Gout: Implications for the Present and Future

  • Ronald L. George
  • Robert T. KeenanEmail author
Part of the following topical collections:
  1. Topical Collection on Crystal Arthritis


Gout is the most common inflammatory arthropathy and occurs in the setting of elevated serum urate levels. Gout is also known to be associated with multiple comorbidities including cardiovascular disease and the metabolic syndrome. Recent advances in research have increased our understanding and improved our knowledge of the pathophysiology of gout. Genome-wide association studies have permitted the identification of several new and common genetic factors that contribute to hyperuricemia and gout. Most of these are involved with the renal urate transport system (the uric acid transportasome), generally considered the most influential regulator of serum urate homeostasis. Thus far, SCL22A12, SCL2A9, and GLUT9 have been found to have the greatest variation and most influence on serum urate levels. However, genetics are only a part of the explanation in the development of hyperuricemia and gout. As results have been mixed, the role of known urate influential genes in gout’s associated comorbidities remains unclear. Regardless, GWAS findings have expanded our understanding of the pathophysiology of hyperuricemia and gout, and will likely play a role in the development of future therapies and treatment of this ancient disease.


Gout Genetics Hyperuricemia Urate transporters Crystal arthritis Therapy Renal urate homeostasis Management Medication safety 



Dr. Keenan has served as a consultant for Savient and Novartis; has received grant support from Novartis; and has received payment for development of educational presentations (including service on speakers’ bureaus) from Savient, Novartis, Amgen, Abbott Laboratories, and Genentech.

Dr. George reported no potential conflicts of interest relevant to this article.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    • Zhu Y, Pandya BJ, Choi HK. Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007–2008. Arthritis Rheum. 2011;63(10):3136–41. Important epidemiological report regarding the prevalence of gout and hyperuricemia in the U.S.PubMedCrossRefGoogle Scholar
  2. 2.
    Oda M, Satta Y, Takenaka O, Takahata N. Loss of urate oxidase activity in hominoids and its evolutionary implications. Mol Biol Evol. 2002;19(5):640–53.PubMedCrossRefGoogle Scholar
  3. 3.
    Shi Y, Evans JE, Rock KL. Molecular identification of a danger signal that alerts the immune system to dying cells. Nature. 2003;425(6957):516–21.PubMedCrossRefGoogle Scholar
  4. 4.
    Johnson RJ, Kang DH, Feig D, Kivlighn S, Kanellis J, Watanabe S, et al. Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease? Hypertension. 2003;41(6):1183–90.PubMedCrossRefGoogle Scholar
  5. 5.
    Ames BN, Cathcart R, Schwiers E, Hochstein P. Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis. Proc Natl Acad Sci U S A. 1981;78(11):6858–62.PubMedCrossRefGoogle Scholar
  6. 6.
    Stecher RM, Hersh AH, Solomon WM. The heredity of gout and its relationship to familial hyperuricemia. Ann Intern Med. 1949;31(4):595–614.PubMedGoogle Scholar
  7. 7.
    Reed DR, Price RA. X-linkage does not account for the absence of father-son similarity in plasma uric acid concentrations. Am J Med Genet. 2000;92(2):142–6.PubMedCrossRefGoogle Scholar
  8. 8.
    Emmerson BT, Nagel SL, Duffy DL, Martin NG. Genetic control of the renal clearance of urate: a study of twins. Ann Rheum Dis. 1992;51(3):375–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Wilk JB, Djousse L, Borecki I, Atwood LD, Hunt SC, Rich SS, et al. Segregation analysis of serum uric acid in the NHLBI Family Heart Study. Hum Genet. 2000;106(3):355–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Lesch M, Nyhan WL. A familial disorder of uric acid metabolism and central nervous system function. Am J Med. 1964;36:561–70.PubMedCrossRefGoogle Scholar
  11. 11.
    Kelley WN, Greene ML, Rosenbloom FM, Henderson JF, Seegmiller JE. Hypoxanthine-guanine phosphoribosyltransferase deficiency in gout. Ann Intern Med. 1969;70(1):155–206.PubMedGoogle Scholar
  12. 12.
    Bleyer AJ, Hart PS, Kmoch S. Hereditary interstitial kidney disease. Semin Nephrol. 2010;30(4):366–73.PubMedCrossRefGoogle Scholar
  13. 13.
    Zivna M, Hulkova H, Matignon M, Hodanova K, Vylet'al P, Kalbacova M, et al. Dominant renin gene mutations associated with early-onset hyperuricemia, anemia, and chronic kidney failure. Am J Hum Genet. 2009;85(2):204–13.PubMedCrossRefGoogle Scholar
  14. 14.
    Mineo I, Kono N, Hara N, Shimizu T, Yamada Y, Kawachi M, et al. Myogenic hyperuricemia. A common pathophysiologic feature of glycogenosis types III, V, and VII. N Engl J Med. 1987;317(2):75–80.PubMedCrossRefGoogle Scholar
  15. 15.
    Sulem P, Gudbjartsson DF, Walters GB, Helgadottir HT, Helgason A, Gudjonsson SA, et al. Identification of low-frequency variants associated with gout and serum uric acid levels. Nat Genet. 2011;43(11):1127–30.PubMedCrossRefGoogle Scholar
  16. 16.
    Vora S, DiMauro S, Spear D, Harker D, Danon MJ. Characterization of the enzymatic defect in late-onset muscle phosphofructokinase deficiency. New subtype of glycogen storage disease type VII. J Clin Invest. 1987;80(5):1479–85.PubMedCrossRefGoogle Scholar
  17. 17.
    Davidson-Mundt A, Luder AS, Greene CL. Hyperuricemia in medium-chain acyl-coenzyme A dehydrogenase deficiency. J Pediatr. 1992;120(3):444–6.PubMedCrossRefGoogle Scholar
  18. 18.
    Sabina RL, Swain JL, Olanow CW, Bradley WG, Fishbein WN, DiMauro S, et al. Myoadenylate deaminase deficiency. Functional and metabolic abnormalities associated with disruption of the purine nucleotide cycle. J Clin Invest. 1984;73(3):720–30.PubMedCrossRefGoogle Scholar
  19. 19.
    Bertorini TE, Shively V, Taylor B, Palmieri GM, Fox IH. ATP degradation products after ischemic exercise: hereditary lack of phosphorylase or carnitine palmityltransferase. Neurology. 1985;35(9):1355–7.PubMedCrossRefGoogle Scholar
  20. 20.
    Merriman TR, Dalbeth N. The genetic basis of hyperuricaemia and gout. Joint Bone Spine. 2011;78(1):35–40.PubMedCrossRefGoogle Scholar
  21. 21.
    Endou H, Anzai N. Urate transport across the apical membrane of renal proximal tubules. Nucleosides Nucleotides Nucleic Acids. 2008;27(6):578–84.PubMedCrossRefGoogle Scholar
  22. 22.
    So A, Thorens B. Uric acid transport and disease. J Clin Invest. 2010;120(6):1791–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Kolz M, Johnson T, Sanna S, Teumer A, Vitart V, Perola M, et al. Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations. PLoS Genet. 2009;5(6):e1000504.PubMedCrossRefGoogle Scholar
  24. 24.
    Anzai N, Jutabha P, Amonpatumrat-Takahashi S, Sakurai H. Recent advances in renal urate transport: characterization of candidate transporters indicated by genome-wide association studies. Clin Exp Nephrol. 2012;16(1):89–95.PubMedCrossRefGoogle Scholar
  25. 25.
    Torres RJ, De Miguel E, Bailen R, Puig JG. Absence of SLC22A12/URAT1 Gene Mutations in Patients with Primary Gout. J Rheumatol. 2012;39(9):1901.Google Scholar
  26. 26.
    Enomoto A, Kimura H, Chairoungdua A, Shigeta Y, Jutabha P, Cha SH, et al. Molecular identification of a renal urate anion exchanger that regulates blood urate levels. Nature. 2002;417(6887):447–52.PubMedGoogle Scholar
  27. 27.
    Ichida K, Hosoyamada M, Hisatome I, Enomoto A, Hikita M, Endou H, et al. Clinical and molecular analysis of patients with renal hypouricemia in Japan-influence of URAT1 gene on urinary urate excretion. J Am Soc Nephrol. 2004;15(1):164–73.PubMedCrossRefGoogle Scholar
  28. 28.
    Cheong HI, Kang JH, Lee JH, Ha IS, Kim S, Komoda F, et al. Mutational analysis of idiopathic renal hypouricemia in Korea. Pediatr Nephrol. 2005;20(7):886–90.PubMedCrossRefGoogle Scholar
  29. 29.
    Dinour D, Bahn A, Ganon L, Ron R, Geifman-Holtzman O, Knecht A, et al. URAT1 mutations cause renal hypouricemia type 1 in Iraqi Jews. Nephrol Dial Transplant. 2011;26(7):2175–81.Google Scholar
  30. 30.
    Sebesta I, Stiburkova B, Bartl J, Ichida K, Hosoyamada M, Taylor J, et al. Diagnostic tests for primary renal hypouricemia. Nucleosides Nucleotides Nucleic Acids. 2011;30(12):1112–6.Google Scholar
  31. 31.
    Shima Y, Teruya K, Ohta H. Association between intronic SNP in urate-anion exchanger gene, SLC22A12, and serum uric acid levels in Japanese. Life Sci. 2006;79(23):2234–7.PubMedCrossRefGoogle Scholar
  32. 32.
    Graessler J, Graessler A, Unger S, Kopprasch S, Tausche AK, Kuhlisch E, et al. Association of the human urate transporter 1 with reduced renal uric acid excretion and hyperuricemia in a German Caucasian population. Arthritis Rheum. 2006;54(1):292–300.PubMedCrossRefGoogle Scholar
  33. 33.
    Tu HP, Chen CJ, Lee CH, Tovosia S, Ko AM, Wang SJ, et al. The SLC22A12 gene is associated with gout in Han Chinese and Solomon Islanders. Ann Rheum Dis. 2010;69(6):1252–4.PubMedCrossRefGoogle Scholar
  34. 34.
    Guan M, Zhang J, Chen Y, Liu W, Kong N, Zou H. High-resolution melting analysis for the rapid detection of an intronic single nucleotide polymorphism in SLC22A12 in male patients with primary gout in China. Scand J Rheumatol. 2009;38(4):276–81.PubMedCrossRefGoogle Scholar
  35. 35.
    Tin A, Woodward OM, Kao WH, Liu CT, Lu X, Nalls MA, et al. Genome-wide association study for serum urate concentrations and gout among African Americans identifies genomic risk loci and a novel URAT1 loss-of-function allele. Hum Mol Genet. 2011;20(20):4056–68.PubMedCrossRefGoogle Scholar
  36. 36.
    Vazquez-Mellado J, Jimenez-Vaca AL, Cuevas-Covarrubias S, Alvarado-Romano V, Pozo-Molina G, Burgos-Vargas R. Molecular analysis of the SLC22A12 (URAT1) gene in patients with primary gout. Rheumatology (Oxford). 2007;46(2):215–9.CrossRefGoogle Scholar
  37. 37.
    • Yang Q, Kottgen A, Dehghan A, Smith AV, Glazer NL, Chen MH, et al. Multiple genetic loci influence serum urate levels and their relationship with gout and cardiovascular disease risk factors. Circ Cardiovasc Genet. 2010;3(6):523–30. A GWAS report that does not support (non-causal) the role of urate (transporters) in gout-associated comorbidities such as cardiovascular disease the metabolic syndrome.PubMedCrossRefGoogle Scholar
  38. 38.
    Doblado M, Moley KH. Facilitative glucose transporter 9, a unique hexose and urate transporter. Am J Physiol Endocrinol Metab. 2009;297(4):E831–5.PubMedCrossRefGoogle Scholar
  39. 39.
    Li S, Sanna S, Maschio A, Busonero F, Usala G, Mulas A, et al. The GLUT9 gene is associated with serum uric acid levels in Sardinia and Chianti cohorts. PLoS Genet. 2007;3(11):e194.PubMedCrossRefGoogle Scholar
  40. 40.
    Phay JE, Hussain HB, Moley JF. Cloning and expression analysis of a novel member of the facilitative glucose transporter family, SLC2A9 (GLUT9). Genomics. 2000;66(2):217–20.PubMedCrossRefGoogle Scholar
  41. 41.
    •• Vitart V, Rudan I, Hayward C, Gray NK, Floyd J, Palmer CN, et al. SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout. Nat Genet. 2008;40(4):437–42. The first to report the role of SLC2A9 (GLUT9) and its variants in the role of urate homeostasis.PubMedCrossRefGoogle Scholar
  42. 42.
    Wallace C, Newhouse SJ, Braund P, Zhang F, Tobin M, Falchi M, et al. Genome-wide association study identifies genes for biomarkers of cardiovascular disease: serum urate and dyslipidemia. Am J Hum Genet. 2008;82(1):139–49.PubMedCrossRefGoogle Scholar
  43. 43.
    •• Dehghan A, Kottgen A, Yang Q, Hwang SJ, Kao WL, Rivadeneira F, et al. Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study. Lancet. 2008;372(9654):1953–61. A very good meta-analysis of genes associated with hyperuricemia and gout. Additionally, the first to identify the SNPs in ABCG2 (ABCG2) and SLC17A3 (NPT4) that influence serum urate levels in blacks and whites.PubMedCrossRefGoogle Scholar
  44. 44.
    Ishibashi K, Matsuzaki T, Takata K, Imai M. Identification of a new member of type I Na/phosphate co-transporter in the rat kidney. Nephron Physiol. 2003;94(1):10–8.CrossRefGoogle Scholar
  45. 45.
    Takenaka K, Morgan JA, Scheffer GL, Adachi M, Stewart CF, Sun D, et al. Substrate overlap between Mrp4 and Abcg2/Bcrp affects purine analogue drug cytotoxicity and tissue distribution. Cancer Res. 2007;67(14):6965–72.PubMedCrossRefGoogle Scholar
  46. 46.
    Yamagishi K, Tanigawa T, Kitamura A, Kottgen A, Folsom AR, Iso H. The rs2231142 variant of the ABCG2 gene is associated with uric acid levels and gout among Japanese people. Rheumatology (Oxford). 2010;49(8):1461–5.CrossRefGoogle Scholar
  47. 47.
    Krishnan E, Lienesch D, Kwoh CK. Gout in ambulatory care settings in the United States. J Rheumatol. 2008;35(3):498–501.PubMedGoogle Scholar
  48. 48.
    Matsuo H, Takada T, Ichida K, Nakamura T, Nakayama A, Ikebuchi Y, et al. Common defects of ABCG2, a high-capacity urate exporter, cause gout: a function-based genetic analysis in a Japanese population. Sci Transl Med. 2009;1(5):5ra11.PubMedCrossRefGoogle Scholar
  49. 49.
    • Ichida K, Matsuo H, Takada T, Nakayama A, Murakami K, Shimizu T, et al. Decreased extra-renal urate excretion is a common cause of hyperuricemia. Nat Commun. 2012;3:764. Insightful study regarding urate homeostasis, genetics, and the role of ABCG2 transporter in the gut.PubMedCrossRefGoogle Scholar
  50. 50.
    Woodward OM, Kottgen A, Coresh J, Boerwinkle E, Guggino WB, Kottgen M. Identification of a urate transporter, ABCG2, with a common functional polymorphism causing gout. Proc Natl Acad Sci U S A. 2009;106(25):10338–42.PubMedCrossRefGoogle Scholar
  51. 51.
    Terkeltaub R. Gout. Novel therapies for treatment of gout and hyperuricemia. Arthritis Res Ther. 2009;11(4):236.PubMedCrossRefGoogle Scholar
  52. 52.
    Shah A, Keenan RT. Gout, hyperuricemia, and the risk of cardiovascular disease: cause and effect? Curr Rheumatol Rep. 2010;12(2):118–24.PubMedCrossRefGoogle Scholar
  53. 53.
    Pillinger MH, Goldfarb DS, Keenan RT. Gout and its comorbidities. Bull NYU Hosp Jt Dis. 2010;68(3):199–203.PubMedGoogle Scholar
  54. 54.
    McKeigue PM, Campbell H, Wild S, Vitart V, Hayward C, Rudan I, et al. Bayesian methods for instrumental variable analysis with genetic instruments ('Mendelian randomization'): example with urate transporter SLC2A9 as an instrumental variable for effect of urate levels on metabolic syndrome. Int J Epidemiol. 2010;39(3):907–18.PubMedCrossRefGoogle Scholar
  55. 55.
    Stark K, Reinhard W, Grassl M, Erdmann J, Schunkert H, Illig T, et al. Common polymorphisms influencing serum uric acid levels contribute to susceptibility to gout, but not to coronary artery disease. PLoS One. 2009;4(11):e7729.PubMedCrossRefGoogle Scholar
  56. 56.
    • Parsa A, Brown E, Weir MR, Fink JC, Shuldiner AR, Mitchell BD, et al. Genotype-based changes in serum uric acid affect blood pressure. Kidney Int. 2012;81(5):502–7. A GWAS report supporting SLC2A9 (GLUT9) variants relationship between serum urate and hypertension.PubMedCrossRefGoogle Scholar
  57. 57.
    • Shafiu M, Johnson RJ, Turner ST, Langaee T, Gong Y, Chapman AB, et al. Urate transporter gene SLC22A12 polymorphisms associated with obesity and metabolic syndrome in Caucasians with hypertension. Kidney Blood Press Res. 2012;35(6):477–82. A GWAS report supporting the role (causal) of SLC22A12 (URAT1) in gout associated comorbidities such as the metabolic syndrome.PubMedCrossRefGoogle Scholar
  58. 58.
    Boger WP, Strickland SC. Probenecid (benemid); its uses and side-effects in 2,502 patients. AMA Arch Intern Med. 1955;95(1):83–92.PubMedCrossRefGoogle Scholar
  59. 59.
    Tan PK, Hyndman D, Liu S, Quart BD, Miner JN. Lesinurad (RDEA594), a novel investigation uricosuric agent for hyperuricemia and gout, blocks transport of uric acid induced by hydrochlorothiazide. Ann Rheum Dis. 2011;50 Suppl 3:187.Google Scholar
  60. 60.
    Burns CM, Wortmann RL. Gout therapeutics: new drugs for an old disease. Lancet. 2011;377(9760):165–77.Google Scholar
  61. 61.
    Serafini TA, Emerling DE. Tranilast suppresses inflammation induced by monosodium urate (MSU) crystals in vivo. Ann Rheum Dis. 2010;69(Suppl3):664.Google Scholar
  62. 62.
    Sundy JS, Kitt MM, Griffith SG, et al. The combination of tranilast with Allopurinol results in enhanced urate lowering. Arthritis Rheum. 2010;62(10 Supplement):S67.Google Scholar
  63. 63.
    Conn PM, Ulloa-Aguirre A. Pharmacological chaperones for misfolded gonadotropin-releasing hormone receptors. Adv Pharmacol. 2011;62:109–41.PubMedCrossRefGoogle Scholar
  64. 64.
    Loo TW, Clarke DM. Correction of defective protein kinesis of human P-glycoprotein mutants by substrates and modulators. J Biol Chem. 1997;272(2):709–12.PubMedCrossRefGoogle Scholar
  65. 65.
    Loo TW, Bartlett MC, Clarke DM. Rescue of folding defects in ABC transporters using pharmacological chaperones. J Bioenerg Biomembr. 2005;37(6):501–7.PubMedCrossRefGoogle Scholar
  66. 66.
    Polgar O, Ierano C, Tamaki A, Stanley B, Ward Y, Xia D, et al. Mutational analysis of threonine 402 adjacent to the GXXXG dimerization motif in transmembrane segment 1 of ABCG2. Biochemistry. 2010;49(10):2235–45.PubMedCrossRefGoogle Scholar
  67. 67.
    Lang Jr PG. Severe hypersensitivity reactions to allopurinol. South Med J. 1979;72(11):1361–8.PubMedCrossRefGoogle Scholar
  68. 68.
    Khanna D, Fuldeore MJ, Meissner BL, Dabbous OH, D'Souza AO. The incidence of Allopurinol hypersensitivity syndrome: a popluation perspective. Arthritis Rheum. 2008;60(10 (Supplement)):S542.Google Scholar
  69. 69.
    Hung SI, Chung WH, Liou LB, Chu CC, Lin M, Huang HP, et al. HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci U S A. 2005;102(11):4134–9.PubMedCrossRefGoogle Scholar
  70. 70.
    Tassaneeyakul W, Jantararoungtong T, Chen P, Lin PY, Tiamkao S, Khunarkornsiri U, et al. Strong association between HLA-B*5801 and allopurinol-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in a Thai population. Pharmacogenet Genomics. 2009;19(9):704–9.PubMedCrossRefGoogle Scholar
  71. 71.
    Lonjou C, Borot N, Sekula P, Ledger N, Thomas L, Halevy S, et al. A European study of HLA-B in Stevens-Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs. Pharmacogenet Genomics. 2008;18(2):99–107.PubMedCrossRefGoogle Scholar
  72. 72.
    Khanna D, Fitzgerald JD, Khanna PP, Bae S, Singh MK, Neogi T, et al. American college of rheumatology guidelines for management of gout. Part 1: systematic Nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken). 2012;64(10):1431–46.CrossRefGoogle Scholar
  73. 73.
    Doring A, Gieger C, Mehta D, Gohlke H, Prokisch H, Coassin S, et al. SLC2A9 influences uric acid concentrations with pronounced sex-specific effects. Nat Genet. 2008;40(4):430–6.PubMedCrossRefGoogle Scholar
  74. 74.
    Brandstatter A, Kiechl S, Kollerits B, Hunt SC, Heid IM, Coassin S, et al. Sex-specific association of the putative fructose transporter SLC2A9 variants with uric acid levels is modified by BMI. Diabetes Care. 2008;31(8):1662–7.PubMedCrossRefGoogle Scholar
  75. 75.
    Hollis-Moffatt JE, Xu X, Dalbeth N, Merriman ME, Topless R, Waddell C, et al. 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. 2009;60(11):3485–92.PubMedCrossRefGoogle Scholar
  76. 76.
    Karns R, Zhang G, Sun G, Rao Indugula S, Cheng H, Havas-Augustin D, et al. Genome-wide association of serum uric acid concentration: replication of sequence variants in an island population of the Adriatic coast of Croatia. Ann Hum Genet. 2012;76(2):121–7.PubMedCrossRefGoogle Scholar
  77. 77.
    Stark K, Reinhard W, Neureuther K, Wiedmann S, Sedlacek K, Baessler A, et al. Association of common polymorphisms in GLUT9 gene with gout but not with coronary artery disease in a large case–control study. PLoS One. 2008;3(4):e1948.PubMedCrossRefGoogle Scholar
  78. 78.
    Charles BA, Shriner D, Doumatey A, Chen G, Zhou J, Huang H, et al. A genome-wide association study of serum uric acid in African Americans. BMC Med Genomics. 2011;4:17.PubMedCrossRefGoogle Scholar
  79. 79.
    McArdle PF, Parsa A, Chang YP, Weir MR, O'Connell JR, Mitchell BD, et al. Association of a common nonsynonymous variant in GLUT9 with serum uric acid levels in old order amish. Arthritis Rheum. 2008;58(9):2874–81.PubMedCrossRefGoogle Scholar
  80. 80.
    Wang B, Miao Z, Liu S, Wang J, Zhou S, Han L, et al. Genetic analysis of ABCG2 gene C421A polymorphism with gout disease in Chinese Han male population. Hum Genet. 2010;127(2):245–6.PubMedCrossRefGoogle Scholar
  81. 81.
    Phipps-Green AJ, Hollis-Moffatt JE, Dalbeth N, Merriman ME, Topless R, Gow PJ, et al. A strong role for the ABCG2 gene in susceptibility to gout in New Zealand Pacific Island and Caucasian, but not Maori, case and control sample sets. Hum Mol Genet. 2010;19(24):4813–9.PubMedCrossRefGoogle Scholar
  82. 82.
    Caulfield MJ, Munroe PB, O'Neill D, Witkowska K, Charchar FJ, Doblado M, et al. SLC2A9 is a high-capacity urate transporter in humans. PLoS Med. 2008;5(10):e197.PubMedCrossRefGoogle Scholar
  83. 83.
    Urano W, Taniguchi A, Anzai N, Inoue E, Kanai Y, Yamanaka M, et al. Sodium-dependent phosphate cotransporter type 1 sequence polymorphisms in male patients with gout. Ann Rheum Dis. 2010;69(6):1232–4.PubMedCrossRefGoogle Scholar
  84. 84.
    van der Harst P, Bakker SJ, de Boer RA, Wolffenbuttel BH, Johnson T, Caulfield MJ, et al. Replication of the five novel loci for uric acid concentrations and potential mediating mechanisms. Hum Mol Genet. 2010;19(2):387–95.PubMedCrossRefGoogle Scholar
  85. 85.
    Li C, Han L, Levin AM, Song H, Yan S, Wang Y, et al. Multiple single nucleotide polymorphisms in the human urate transporter 1 (hURAT1) gene are associated with hyperuricaemia in Han Chinese. J Med Genet. 2010;47(3):204–10.PubMedCrossRefGoogle Scholar
  86. 86.
    Jang WC, Nam YH, Park SM, Ahn YC, Park SH, Choe JY, et al. T6092C polymorphism of SLC22A12 gene is associated with serum uric acid concentrations in Korean male subjects. Clin Chim Acta. 2008;398(1–2):140–4.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Division of Rheumatology and ImmunologyDuke University School of MedicineDurhamUSA

Personalised recommendations