Pleiotropic effect of the ABCG2 gene in gout: involvement in serum urate levels and progression from hyperuricemia to gout
Abstract Background The ABCG2 Q141K (rs2231142) and rs10011796 variants associate with hyperuricaemia (HU). The effect size of ABCG2 rs2231142 on urate is ~ 60% that of SLC2A9, yet the effect size on gout is greater. We tested the hypothesis that ABCG2 plays a role in the progression from HU to gout...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-03-01
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| Series: | Arthritis Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13075-020-2136-z |
| _version_ | 1818294007769333760 |
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| author | Rebekah Wrigley Amanda J. Phipps-Green Ruth K. Topless Tanya J. Major Murray Cadzow Philip Riches Anne-Kathrin Tausche Matthijs Janssen Leo A. B. Joosten Tim L. Jansen Alexander So Jennie Harré Hindmarsh Lisa K. Stamp Nicola Dalbeth Tony R. Merriman |
| author_facet | Rebekah Wrigley Amanda J. Phipps-Green Ruth K. Topless Tanya J. Major Murray Cadzow Philip Riches Anne-Kathrin Tausche Matthijs Janssen Leo A. B. Joosten Tim L. Jansen Alexander So Jennie Harré Hindmarsh Lisa K. Stamp Nicola Dalbeth Tony R. Merriman |
| author_sort | Rebekah Wrigley |
| collection | DOAJ |
| description | Abstract Background The ABCG2 Q141K (rs2231142) and rs10011796 variants associate with hyperuricaemia (HU). The effect size of ABCG2 rs2231142 on urate is ~ 60% that of SLC2A9, yet the effect size on gout is greater. We tested the hypothesis that ABCG2 plays a role in the progression from HU to gout by testing for association of ABCG2 rs2231142 and rs10011796 with gout using HU controls. Methods We analysed 1699 European gout cases and 14,350 normouricemic (NU) and HU controls, and 912 New Zealand (NZ) Polynesian (divided into Eastern and Western Polynesian) gout cases and 696 controls. Association testing was performed using logistic and linear regression with multivariate adjusting for confounding variables. Results In Europeans and Polynesians, the ABCG2 141K (T) allele was associated with gout using HU controls (OR = 1.85, P = 3.8E− 21 and ORmeta = 1.85, P = 1.3E− 03, respectively). There was evidence for an effect of 141K in determining HU in European (OR = 1.56, P = 1.7E− 18) but not in Polynesian (ORmeta = 1.49, P = 0.057). For SLC2A9 rs11942223, the T allele associated with gout in the presence of HU in European (OR = 1.37, P = 4.7E− 06), however significantly weaker than ABCG2 rs2231142 141K (P Het = 0.0023). In Western Polynesian and European, there was epistatic interaction between ABCG2 rs2231142 and rs10011796. Combining the presence of the 141K allele with the rs10011796 CC-genotype increased gout risk, in the presence of HU, 21.5-fold in Western Polynesian (P = 0.009) and 2.6-fold in European (P = 9.9E− 06). The 141K allele of ABCG2 associated with increased gout flare frequency in Polynesian (P meta = 2.5E− 03). Conclusion These data are consistent with a role for ABCG2 141K in gout in the presence of established HU. |
| first_indexed | 2024-12-13T03:24:54Z |
| format | Article |
| id | doaj.art-88e69affacaf42ba8bbee5b52156c6c7 |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-12-13T03:24:54Z |
| publishDate | 2020-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-88e69affacaf42ba8bbee5b52156c6c72022-12-22T00:01:18ZengBMCArthritis Research & Therapy1478-63622020-03-0122111010.1186/s13075-020-2136-zPleiotropic effect of the ABCG2 gene in gout: involvement in serum urate levels and progression from hyperuricemia to goutRebekah Wrigley0Amanda J. Phipps-Green1Ruth K. Topless2Tanya J. Major3Murray Cadzow4Philip Riches5Anne-Kathrin Tausche6Matthijs Janssen7Leo A. B. Joosten8Tim L. Jansen9Alexander So10Jennie Harré Hindmarsh11Lisa K. Stamp12Nicola Dalbeth13Tony R. Merriman14Department of Biochemistry, University of OtagoDepartment of Biochemistry, University of OtagoDepartment of Biochemistry, University of OtagoDepartment of Biochemistry, University of OtagoDepartment of Biochemistry, University of OtagoRheumatic Diseases Unit, Institute of Genetics and Molecular Medicine, University of EdinburghDepartment of Rheumatology, University Clinic “Carl-Gustav-Carus”Department of Rheumatology, VieCuri Medical CenterDepartment of Internal Medicine and Radboud Institute of Molecular Life Science, Radboud University Medical CenterDepartment of Rheumatology, VieCuri Medical CenterLaboratory of Rheumatology, University of Lausanne, CHUVNgāti Porou Hauora Charitable TrustDepartment of Medicine, University of Otago, ChristchurchDepartment of Medicine, University of AucklandDepartment of Biochemistry, University of OtagoAbstract Background The ABCG2 Q141K (rs2231142) and rs10011796 variants associate with hyperuricaemia (HU). The effect size of ABCG2 rs2231142 on urate is ~ 60% that of SLC2A9, yet the effect size on gout is greater. We tested the hypothesis that ABCG2 plays a role in the progression from HU to gout by testing for association of ABCG2 rs2231142 and rs10011796 with gout using HU controls. Methods We analysed 1699 European gout cases and 14,350 normouricemic (NU) and HU controls, and 912 New Zealand (NZ) Polynesian (divided into Eastern and Western Polynesian) gout cases and 696 controls. Association testing was performed using logistic and linear regression with multivariate adjusting for confounding variables. Results In Europeans and Polynesians, the ABCG2 141K (T) allele was associated with gout using HU controls (OR = 1.85, P = 3.8E− 21 and ORmeta = 1.85, P = 1.3E− 03, respectively). There was evidence for an effect of 141K in determining HU in European (OR = 1.56, P = 1.7E− 18) but not in Polynesian (ORmeta = 1.49, P = 0.057). For SLC2A9 rs11942223, the T allele associated with gout in the presence of HU in European (OR = 1.37, P = 4.7E− 06), however significantly weaker than ABCG2 rs2231142 141K (P Het = 0.0023). In Western Polynesian and European, there was epistatic interaction between ABCG2 rs2231142 and rs10011796. Combining the presence of the 141K allele with the rs10011796 CC-genotype increased gout risk, in the presence of HU, 21.5-fold in Western Polynesian (P = 0.009) and 2.6-fold in European (P = 9.9E− 06). The 141K allele of ABCG2 associated with increased gout flare frequency in Polynesian (P meta = 2.5E− 03). Conclusion These data are consistent with a role for ABCG2 141K in gout in the presence of established HU.http://link.springer.com/article/10.1186/s13075-020-2136-zGoutUrateHyperuricemiaABCG2AssociationPolymorphism |
| spellingShingle | Rebekah Wrigley Amanda J. Phipps-Green Ruth K. Topless Tanya J. Major Murray Cadzow Philip Riches Anne-Kathrin Tausche Matthijs Janssen Leo A. B. Joosten Tim L. Jansen Alexander So Jennie Harré Hindmarsh Lisa K. Stamp Nicola Dalbeth Tony R. Merriman Pleiotropic effect of the ABCG2 gene in gout: involvement in serum urate levels and progression from hyperuricemia to gout Arthritis Research & Therapy Gout Urate Hyperuricemia ABCG2 Association Polymorphism |
| title | Pleiotropic effect of the ABCG2 gene in gout: involvement in serum urate levels and progression from hyperuricemia to gout |
| title_full | Pleiotropic effect of the ABCG2 gene in gout: involvement in serum urate levels and progression from hyperuricemia to gout |
| title_fullStr | Pleiotropic effect of the ABCG2 gene in gout: involvement in serum urate levels and progression from hyperuricemia to gout |
| title_full_unstemmed | Pleiotropic effect of the ABCG2 gene in gout: involvement in serum urate levels and progression from hyperuricemia to gout |
| title_short | Pleiotropic effect of the ABCG2 gene in gout: involvement in serum urate levels and progression from hyperuricemia to gout |
| title_sort | pleiotropic effect of the abcg2 gene in gout involvement in serum urate levels and progression from hyperuricemia to gout |
| topic | Gout Urate Hyperuricemia ABCG2 Association Polymorphism |
| url | http://link.springer.com/article/10.1186/s13075-020-2136-z |
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