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Open Access 01-04-2012 | Research article

The renal urate transporter SLC17A1 locus: confirmation of association with gout

Authors: Jade E Hollis-Moffatt, Amanda J Phipps-Green, Brett Chapman, Gregory T Jones, Andre van Rij, Peter J Gow, Andrew A Harrison, John Highton, Peter B Jones, Grant W Montgomery, Lisa K Stamp, Nicola Dalbeth, Tony R Merriman

Published in: Arthritis Research & Therapy | Issue 2/2012

Abstract

Introduction

Two major gout-causing genes have been identified, the urate transport genes SLC2A9 and ABCG2. Variation within the SLC17A1 locus, which encodes sodium-dependent phosphate transporter 1, a renal transporter of uric acid, has also been associated with serum urate concentration. However, evidence for association with gout is equivocal. We investigated the association of the SLC17A1 locus with gout in New Zealand sample sets.

Methods

Five variants (rs1165196, rs1183201, rs9358890, rs3799344, rs12664474) were genotyped across a New Zealand sample set totaling 971 cases and 1,742 controls. Cases were ascertained according to American Rheumatism Association criteria. Two population groups were studied: Caucasian and Polynesian.

Results

At rs1183201 (SLC17A1), evidence for association with gout was observed in both the Caucasian (odds ratio (OR) = 0.67, P = 3.0 × 10^-6) and Polynesian (OR = 0.74, P = 3.0 × 10^-3) groups. Meta-analysis confirmed association of rs1183201 with gout at a genome-wide level of significance (OR = 0.70, P = 3.0 × 10^-8). Haplotype analysis suggested the presence of a common protective haplotype.

Conclusion

We confirm the SLC17A1 locus as the third associated with gout at a genome-wide level of significance.

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Simmonds HA, McBride MB, Hatfield PJ, Graham R, McCaskey J, Jackson M: Polynesian women are also at risk for hyperuricaemia and gout because of a genetic defect in renal urate handling. Br J Rheumatol. 1994, 33: 932-937. 10.1093/rheumatology/33.10.932.CrossRefPubMed

Merriman TR, Dalbeth N: The genetic basis of hyperuricaemia and gout. Joint Bone Spine. 2011, 38: 35-40.CrossRef

Kolz M, Johnson T, Sanna S, Teumer A, Vitart V, Perola M, Mangino M, Albrecht E, Wallace C, Farrall M, Johansson A, Nyholt DR, Aulchenko Y, Beckmann JS, Bergmann S, Bochud M, Brown M, Campbell H, EUROSPAN Consortium, Connell J, Dominiczak A, Homuth G, Lamina C, McCarthy MI, ENGAGE Consortium, Meitinger T, Mooser V, Munroe P, Nauck M, Peden J, et al: Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations. PLoS Genet. 2009, 5: e1000504-10.1371/journal.pgen.1000504.CrossRefPubMed

Yang Q, Kottgen A, Dehghan A, Smith AV, Glazer NL, Chen MH, Chasman DI, Aspelund T, Eiriksdottir G, Harris TB, Launer L, Nalls M, Hernandez D, Arking DE, Boerwinkle E, Grove ML, Li M, Linda Kao WH, Chonchol M, Haritunians T, Li G, Lumley T, Psaty BM, Shlipak M, Hwang SJ, Larson MG, O'Donnell CJ, Upadhyay A, van Duijn CM, et al: Multiple genetic loci influence serum urate and their relationship with gout and cardiovascular disease risk factors. Circ Cardiovasc Genet. 2010, 3: 523-530. 10.1161/CIRCGENETICS.109.934455.CrossRefPubMed

Busch AE, Schuster A, Waldegger S, Wagner CA, Zempel G, Broer S, Biber J, Murer H, Lang F: Expression of a renal type I sodium/phosphate transporter (NaPi-1) induces a conductance in Xenopus oocytes permeable for organic and inorganic anions. Proc Natl Acad Sci USA. 1996, 93: 5347-5351. 10.1073/pnas.93.11.5347.CrossRefPubMed

Iharada M, Miyaji T, Fujimoto T, Hiasa M, Anzai N, Omote H, Moriyama Y: Type 1 sodium-dependent phosphate transporter (SLC17A1 protein) is a Cl(-)-dependent urate exporter. J Biol Chem. 2010, 285: 26107-26113. 10.1074/jbc.M110.122721.CrossRefPubMed

Uchino H, Tamai I, Yamashita K, Minemoto Y, Sai Y, Yabuuchi H, Miyamoto K, Takeda E, Tsuji A: p-aminohippuric acid transport at renal apical membrane mediated by human inorganic phosphate transporter NPT1. Biochem Biophys Res Commun. 2000, 270: 254-259. 10.1006/bbrc.2000.2407.CrossRefPubMed

Urano W, Taniguchi A, Anzai N, Inoue E, Kanai Y, Yamanaka M, Endou H, Kamatani N, Yamanaka H: Sodium-dependent phosphate cotransporter type 1 sequence polymorphisms in male patients with gout. Ann Rheum Dis. 2010, 69: 1232-1234. 10.1136/ard.2008.106856.CrossRefPubMed

Dehghan A, Köttgen A, Yang Q, Hwang SJ, Kao WL, Rivadeneira F, Boerwinkle E, Levy D, Hofman A, Astor BC, Benjamin EJ, van Duijn CM, Witteman JC, Coresh J, Fox CS: Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study. Lancet. 2008, 372: 1953-1961. 10.1016/S0140-6736(08)61343-4.CrossRefPubMed

10.

Stark K, Reinhard W, Grassl M, Erdmann J, Schunkert H, Illig T, Hengstenberg C: Common polymorphisms influencing serum uric acid levels contribute to susceptibility to gout, but not to coronary artery disease. PLoS One. 2009, 4: e7729-10.1371/journal.pone.0007729.CrossRefPubMed

11.

Roberts RL, Van Rij AM, Phillips LV, Young S, McCormick SP, Merriman TR, Jones GT: Interaction of the inflammasome genes CARD8 and NLRP3 in abdominal aortic aneurysms. Atherosclerosis. 2011, 218: 123-126. 10.1016/j.atherosclerosis.2011.04.043.CrossRefPubMed

12.

Gretarsdottir S, Baas AF, Thorleifsson G, Holm H, den Heijer M, de Vries JP, Kranendonk SE, Zeebregts CJ, van Sterkenburg SM, Geelkerken RH, van Rij AM, Williams MJ, Boll AP, Kostic JP, Jonasdottir A, Jonasdottir A, Walters GB, Masson G, Sulem P, Saemundsdottir J, Mouy M, Magnusson KP, Tromp G, Elmore JR, Sakalihasan N, Limet R, Defraigne JO, Ferrell RE, Ronkainen A, Ruigrok YM: Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm. Nat Genet. 2010, 42: 692-697. 10.1038/ng.622.CrossRefPubMed

13.

Wallace SL, Robinson H, Masi AT, Decker JL, McCarty DJ, Yu TF: Preliminary criteria for the classification of the acute arthritis of primary gout. Arthritis Rheum. 1977, 20: 895-900. 10.1002/art.1780200320.CrossRefPubMed

14.

Friedlaender JS, Friedlaender FR, Reed FA, Kidd KK, Kidd JR, Chambers GK, Lea RA, Loo JH, Koki G, Hodgson JA, Merriwether DA, Weber JL: The genetic structure of Pacific Islanders. PLoS Genet. 2008, 4: e19-10.1371/journal.pgen.0040019.CrossRefPubMed

15.

Wollstein A, Lao O, Becker C, Brauer S, Trent RJ, Nürnberg P, Stoneking M, Kayser M: Demographic history of Oceania inferred from genome-wide data. Curr Biol. 2010, 20: 1983-1992. 10.1016/j.cub.2010.10.040.CrossRefPubMed

16.

Phipps-Green AJ, Hollis-Moffatt JE, Dalbeth N, Merriman ME, Topless R, Gow PJ, Harrison AA, Highton J, Jones PB, Stamp LK, Merriman TR: 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: 4813-4819. 10.1093/hmg/ddq412.CrossRefPubMed

17.

Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC: PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007, 81: 559-575. 10.1086/519795.CrossRefPubMed

18.

Winnard D, Wright C, Taylor WJ, Jackson G, Te Karu L, Gow PJ, Arroll B, Thornley S, Gribben B, Dalbeth D: National prevalence of gout derived from administrative health data in Aotearoa New Zealand. Rheumatology. 2012, 51: 901-909. 10.1093/rheumatology/ker361.CrossRefPubMed

19.

Pritchard JK, Stephens M, Donnelly P: Inference of population structure using multilocus genotype data. Genetics. 2000, 155: 945-959.PubMed

20.

Hollis-Moffatt JE, Xu X, Dalbeth N, Merriman ME, Topless R, Waddell C, Gow PJ, Harrison AA, Highton J, Jones PB, Stamp LK, Merriman TR: 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: 3485-3492. 10.1002/art.24938.CrossRefPubMed

21.

Choi HK, Atkinson K, Karlson EW, Willett W, Curhan G: Purine-rich foods, dairy and protein intake, and the risk of gout in men. N Engl J Med. 2004, 350: 1093-1103. 10.1056/NEJMoa035700.CrossRefPubMed

22.

McAdams MA, Maynard JW, Baer AN, Köttgen A, Clipp S, Coresh J, Gelber AC: Reliability and sensitivity of the self-report of physician-diagnosed gout in the campaign against cancer and heart disease and the atherosclerosis risk in the community cohorts. J Rheumatol. 2011, 38: 135-141. 10.3899/jrheum.100418.CrossRefPubMed

23.

Harrold LR, Saag KG, Yood RA, Mikuls TR, Andrade SE, Fouayzi H, Davis J, Chan KA, Raebel MA, Von Worley A, Platt R: Validity of gout diagnoses in administrative data. Arthritis Rheum. 2007, 57: 103-108. 10.1002/art.22474.CrossRefPubMed

24.

Roddy E, Doherty M: Epidemiology of gout. Arthritis Res Ther. 2010, 12: 223-10.1186/ar3199.CrossRefPubMed

25.

Hagos Y, Stein D, Ugele B, Burckhardt G, Bahn A: Human renal organic anion transporter 4 operates as an asymmetric urate transporter. J Am Soc Nephrol. 2007, 18: 430-439. 10.1681/ASN.2006040415.CrossRefPubMed

26.

Jutabha P, Anzai N, Kitamura K, Taniguchi A, Kaneko S, Yan K, Yamada H, Shimada H, Kimura T, Katada T, Fukutomi T, Tomita K, Urano W, Yamanaka H, Seki G, Fujita T, Moriyama Y, Yamada A, Uchida S, Wempe MF, Endou H, Sakurai H: Human sodium phosphate transporter 4 (hNPT4/SLC17A3) as a common renal secretory pathway for drugs and urate. J Biol Chem. 2010, 285: 35123-35123. 10.1074/jbc.M110.121301.CrossRefPubMed

Title: The renal urate transporter SLC17A1 locus: confirmation of association with gout
Authors: Jade E Hollis-Moffatt
Amanda J Phipps-Green
Brett Chapman
Gregory T Jones
Andre van Rij
Peter J Gow
Andrew A Harrison
John Highton
Peter B Jones
Grant W Montgomery
Lisa K Stamp
Nicola Dalbeth
Tony R Merriman
Publication date: 01-04-2012
Publisher: BioMed Central
Published in: Arthritis Research & Therapy / Issue 2/2012
Electronic ISSN: 1478-6362
DOI: https://doi.org/10.1186/ar3816

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