Humaira Rasheed1, Amanda J Phipps-Green2, Ruth Topless2, Malcolm D Smith3, Catherine Hill4, Susan Lester4, Maureen Rischmueller4, Matthijs Janssen5, Timothy L Jansen6, Leo A Joosten7, Timothy R Radstake8, Philip L Riches9, Anne-Kathrin Tausche10, Frederic Lioté11, Alexander So12, Andre van Rij13, Gregory T Jones13, Sally P McCormick2, Andrew A Harrison14, Lisa K Stamp15, Nicola Dalbeth16, Tony R Merriman17. 1. Department of Biochemistry, University of Otago, Dunedin, New Zealand Department of Chemistry, University of Engineering and Technology, Lahore, Pakistan. 2. Department of Biochemistry, University of Otago, Dunedin, New Zealand. 3. Department of Medicine, Flinders Medical Centre and Repatriation General Hospital, Adelaide. 4. Rheumatology Department, The Queen Elizabeth Hospital, Woodville South, SA, Australia. 5. Department of Rheumatology, Rijnstate Hospital, Arnhem. 6. Department of IQ HealthCare, VieCuri Medical Centre, Venlo. 7. Department of Internal Medicine and Radboud Institute of Molecular Life Science, Radboud University Medical Center, Nijmegen. 8. Department of Rheumatology and Clinical Immunology, Laboratory of Translational Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands. 9. Rheumatic Diseases Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK. 10. Department of Rheumatology, University Clinic Carl-Gustav-Carus, Dresden, Germany. 11. INSERM, UMR-S 1132, Hospital Lariboisière University Paris Diderot (UFR de Médecine), Sorbonne Paris Cité, Paris, F-75205, France. 12. DAL, Service of Rheumatology, Laboratory of Rheumatology, University of Lausanne, CHUV, Nestlé 05-5029, Lausanne, Switzerland. 13. Department of Surgery, University of Otago, Dunedin. 14. Department of Medicine, University of Otago, Wellington. 15. Department of Medicine, University of Otago, Christchurch. 16. Department of Medicine, University of Auckland, Auckland, New Zealand. 17. Department of Biochemistry, University of Otago, Dunedin, New Zealand tony.merriman@otago.ac.nz.
Abstract
OBJECTIVE: Gout is associated with dyslipidaemia. Association of the apolipoprotein A1-C3-A4 gene cluster with gout has previously been reported in a small study. To investigate a possible causal role for this locus in gout, we tested the association of genetic variants from APOA1 (rs670) and APOC3 (rs5128) with gout. METHODS: We studied data for 2452 controls and 2690 clinically ascertained gout cases of European and New Zealand Polynesian (Māori and Pacific) ancestry. Data were also used from the publicly available Atherosclerosis Risk in Communities study (n = 5367) and the Framingham Heart Study (n = 2984). Multivariate adjusted logistic and linear regression was used to test the association of single-nucleotide polymorphisms with gout risk, serum urate, triglyceride and high-density lipoprotein cholesterol (HDL-C). RESULTS: In Polynesians, the T-allele of rs670 (APOA1) increased (odds ratio, OR = 1.53, P = 4.9 × 10(-6)) and the G-allele of rs5128 (APOC3) decreased the risk of gout (OR = 0.86, P = 0.026). In Europeans, there was a strong trend to a risk effect of the T-allele for rs670 (OR = 1.11, P = 0.055), with a significant protective effect of the G-allele for rs5128 being observed after adjustment for triglycerides and HDL-C (OR = 0.81, P = 0.039). The effect at rs5128 was specific to males in both Europeans and Polynesians. Association in Polynesians was independent of any effect of rs670 and rs5128 on triglyceride and HDL-C levels. There was no evidence for association of either single-nucleotide polymorphism with serum urate levels (P ⩾ 0.10). CONCLUSION: Our data, replicating a previous study, supports the hypothesis that the apolipoprotein A1-C3-A4 gene cluster plays a causal role in gout.
OBJECTIVE:Gout is associated with dyslipidaemia. Association of the apolipoprotein A1-C3-A4 gene cluster with gout has previously been reported in a small study. To investigate a possible causal role for this locus in gout, we tested the association of genetic variants from APOA1 (rs670) and APOC3 (rs5128) with gout. METHODS: We studied data for 2452 controls and 2690 clinically ascertained gout cases of European and New Zealand Polynesian (Māori and Pacific) ancestry. Data were also used from the publicly available Atherosclerosis Risk in Communities study (n = 5367) and the Framingham Heart Study (n = 2984). Multivariate adjusted logistic and linear regression was used to test the association of single-nucleotide polymorphisms with gout risk, serum urate, triglyceride and high-density lipoprotein cholesterol (HDL-C). RESULTS: In Polynesians, the T-allele of rs670 (APOA1) increased (odds ratio, OR = 1.53, P = 4.9 × 10(-6)) and the G-allele of rs5128 (APOC3) decreased the risk of gout (OR = 0.86, P = 0.026). In Europeans, there was a strong trend to a risk effect of the T-allele for rs670 (OR = 1.11, P = 0.055), with a significant protective effect of the G-allele for rs5128 being observed after adjustment for triglycerides and HDL-C (OR = 0.81, P = 0.039). The effect at rs5128 was specific to males in both Europeans and Polynesians. Association in Polynesians was independent of any effect of rs670 and rs5128 on triglyceride and HDL-C levels. There was no evidence for association of either single-nucleotide polymorphism with serum urate levels (P ⩾ 0.10). CONCLUSION: Our data, replicating a previous study, supports the hypothesis that the apolipoprotein A1-C3-A4 gene cluster plays a causal role in gout.
Authors: J M Ordovas; F Civeira; J Genest; S Craig; A H Robbins; T Meade; M Pocovi; P M Frossard; U Masharani; P W Wilson Journal: Atherosclerosis Date: 1991-03 Impact factor: 5.162
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 Journal: Arthritis Res Ther Date: 2012-04-27 Impact factor: 5.156
Authors: Humaira Rasheed; Angela Hsu; Nicola Dalbeth; Lisa K Stamp; Sally McCormick; Tony R Merriman Journal: Arthritis Res Ther Date: 2014-11-29 Impact factor: 5.156
Authors: Panagiotis Antiochos; Pedro Marques-Vidal; Julien Virzi; Sabrina Pagano; Nathalie Satta; Oliver Hartley; Fabrizio Montecucco; François Mach; Zoltán Kutalik; Gerard Waeber; Peter Vollenweider; Nicolas Vuilleumier Journal: Front Immunol Date: 2017-04-18 Impact factor: 7.561