Kouichi Asano1,2, Motohiro Esaki3, Junji Umeno3, Atsushi Hirano3,4, Yuji Maehata3, Tomohiko Moriyama3, Shotaro Nakamura5, Takayuki Matsumoto6, Takanari Kitazono3. 1. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. k-asano@intmed2.med.kyushu-u.ac.jp. 2. Department of Endoscopic Diagnosis and Therapeutics, Kyushu University Hospital, Fukuoka, Japan. k-asano@intmed2.med.kyushu-u.ac.jp. 3. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. 4. Department of Internal Medicine, Yamaguchi Red Cross Hospital, Yamaguchi, Japan. 5. Department of Advanced Medical Initiatives, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan. 6. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan.
Abstract
BACKGROUND: Recent genome-wide association studies have identified nearly 100 susceptibility genes for ulcerative colitis (UC). However, the contribution of susceptibility variants for UC to clinical outcome has scarcely been reported. The aim of this study was to investigate whether UC-associated genetic variants confer a risk of clinical relapse. METHODS: One hundred and nine consecutive Japanese subjects with quiescent UC were recruited. Four genetic variants of HLA-DRB1*1502, rs6671847 at FCGR2A, rs17085007 at 13q12, and rs2108225 at SLC26A3 were genotyped by Invader assay. The clinical courses were followed after blood sampling, and the risk of relapse according to these genotypes was calculated by Cox proportional hazard model. RESULTS: During the mean follow-up period of 35 months (range 1-81 months), 49 of 109 subjects (45 %) relapsed. Carriers of the G allele of rs6671847 showed an increased risk of relapse compared with non-carriers [adjusted hazard ratio (HR), 2.27; 95 % confidence interval (CI), 1.20-4.32; p = 0.01]. Patients with the CT or TT genotypes of rs17085007 also had an increased risk of relapse compared to subjects with the CC genotype (for CT: adjusted HR, 2.16; 95 % CI, 1.10-4.23; p = 0.03; for TT: adjusted HR, 3.25; 95 % CI, 1.18-8.95; p = 0.02). These two risk variants multiplied the risk of relapse by 2.74 times (95 % CI, 1.10-4.23; p = 0.01) in patients with one risk genotype and 5.40 times (95 % CI, 2.06-14.13; p = 0.0006) in patients with both risk genotypes. CONCLUSIONS: Genetic variants of rs6671847 at FCGR2A and rs17085007 at 13q12 conferred a risk of relapse in patients with UC.
BACKGROUND: Recent genome-wide association studies have identified nearly 100 susceptibility genes for ulcerative colitis (UC). However, the contribution of susceptibility variants for UC to clinical outcome has scarcely been reported. The aim of this study was to investigate whether UC-associated genetic variants confer a risk of clinical relapse. METHODS: One hundred and nine consecutive Japanese subjects with quiescent UC were recruited. Four genetic variants of HLA-DRB1*1502, rs6671847 at FCGR2A, rs17085007 at 13q12, and rs2108225 at SLC26A3 were genotyped by Invader assay. The clinical courses were followed after blood sampling, and the risk of relapse according to these genotypes was calculated by Cox proportional hazard model. RESULTS: During the mean follow-up period of 35 months (range 1-81 months), 49 of 109 subjects (45 %) relapsed. Carriers of the G allele of rs6671847 showed an increased risk of relapse compared with non-carriers [adjusted hazard ratio (HR), 2.27; 95 % confidence interval (CI), 1.20-4.32; p = 0.01]. Patients with the CT or TT genotypes of rs17085007 also had an increased risk of relapse compared to subjects with the CC genotype (for CT: adjusted HR, 2.16; 95 % CI, 1.10-4.23; p = 0.03; for TT: adjusted HR, 3.25; 95 % CI, 1.18-8.95; p = 0.02). These two risk variants multiplied the risk of relapse by 2.74 times (95 % CI, 1.10-4.23; p = 0.01) in patients with one risk genotype and 5.40 times (95 % CI, 2.06-14.13; p = 0.0006) in patients with both risk genotypes. CONCLUSIONS: Genetic variants of rs6671847 at FCGR2A and rs17085007 at 13q12 conferred a risk of relapse in patients with UC.
Authors: Carl A Anderson; Gabrielle Boucher; Charlie W Lees; Andre Franke; Mauro D'Amato; Kent D Taylor; James C Lee; Philippe Goyette; Marcin Imielinski; Anna Latiano; Caroline Lagacé; Regan Scott; Leila Amininejad; Suzannah Bumpstead; Leonard Baidoo; Robert N Baldassano; Murray Barclay; Theodore M Bayless; Stephan Brand; Carsten Büning; Jean-Frédéric Colombel; Lee A Denson; Martine De Vos; Marla Dubinsky; Cathryn Edwards; David Ellinghaus; Rudolf S N Fehrmann; James A B Floyd; Timothy Florin; Denis Franchimont; Lude Franke; Michel Georges; Jürgen Glas; Nicole L Glazer; Stephen L Guthery; Talin Haritunians; Nicholas K Hayward; Jean-Pierre Hugot; Gilles Jobin; Debby Laukens; Ian Lawrance; Marc Lémann; Arie Levine; Cecile Libioulle; Edouard Louis; Dermot P McGovern; Monica Milla; Grant W Montgomery; Katherine I Morley; Craig Mowat; Aylwin Ng; William Newman; Roel A Ophoff; Laura Papi; Orazio Palmieri; Laurent Peyrin-Biroulet; Julián Panés; Anne Phillips; Natalie J Prescott; Deborah D Proctor; Rebecca Roberts; Richard Russell; Paul Rutgeerts; Jeremy Sanderson; Miquel Sans; Philip Schumm; Frank Seibold; Yashoda Sharma; Lisa A Simms; Mark Seielstad; A Hillary Steinhart; Stephan R Targan; Leonard H van den Berg; Morten Vatn; Hein Verspaget; Thomas Walters; Cisca Wijmenga; David C Wilson; Harm-Jan Westra; Ramnik J Xavier; Zhen Z Zhao; Cyriel Y Ponsioen; Vibeke Andersen; Leif Torkvist; Maria Gazouli; Nicholas P Anagnou; Tom H Karlsen; Limas Kupcinskas; Jurgita Sventoraityte; John C Mansfield; Subra Kugathasan; Mark S Silverberg; Jonas Halfvarson; Jerome I Rotter; Christopher G Mathew; Anne M Griffiths; Richard Gearry; Tariq Ahmad; Steven R Brant; Mathias Chamaillard; Jack Satsangi; Judy H Cho; Stefan Schreiber; Mark J Daly; Jeffrey C Barrett; Miles Parkes; Vito Annese; Hakon Hakonarson; Graham Radford-Smith; Richard H Duerr; Séverine Vermeire; Rinse K Weersma; John D Rioux Journal: Nat Genet Date: 2011-02-06 Impact factor: 38.330
Authors: Luke Jostins; Stephan Ripke; Rinse K Weersma; Richard H Duerr; Dermot P McGovern; Ken Y Hui; James C Lee; L Philip Schumm; Yashoda Sharma; Carl A Anderson; Jonah Essers; Mitja Mitrovic; Kaida Ning; Isabelle Cleynen; Emilie Theatre; Sarah L Spain; Soumya Raychaudhuri; Philippe Goyette; Zhi Wei; Clara Abraham; Jean-Paul Achkar; Tariq Ahmad; Leila Amininejad; Ashwin N Ananthakrishnan; Vibeke Andersen; Jane M Andrews; Leonard Baidoo; Tobias Balschun; Peter A Bampton; Alain Bitton; Gabrielle Boucher; Stephan Brand; Carsten Büning; Ariella Cohain; Sven Cichon; Mauro D'Amato; Dirk De Jong; Kathy L Devaney; Marla Dubinsky; Cathryn Edwards; David Ellinghaus; Lynnette R Ferguson; Denis Franchimont; Karin Fransen; Richard Gearry; Michel Georges; Christian Gieger; Jürgen Glas; Talin Haritunians; Ailsa Hart; Chris Hawkey; Matija Hedl; Xinli Hu; Tom H Karlsen; Limas Kupcinskas; Subra Kugathasan; Anna Latiano; Debby Laukens; Ian C Lawrance; Charlie W Lees; Edouard Louis; Gillian Mahy; John Mansfield; Angharad R Morgan; Craig Mowat; William Newman; Orazio Palmieri; Cyriel Y Ponsioen; Uros Potocnik; Natalie J Prescott; Miguel Regueiro; Jerome I Rotter; Richard K Russell; Jeremy D Sanderson; Miquel Sans; Jack Satsangi; Stefan Schreiber; Lisa A Simms; Jurgita Sventoraityte; Stephan R Targan; Kent D Taylor; Mark Tremelling; Hein W Verspaget; Martine De Vos; Cisca Wijmenga; David C Wilson; Juliane Winkelmann; Ramnik J Xavier; Sebastian Zeissig; Bin Zhang; Clarence K Zhang; Hongyu Zhao; Mark S Silverberg; Vito Annese; Hakon Hakonarson; Steven R Brant; Graham Radford-Smith; Christopher G Mathew; John D Rioux; Eric E Schadt; Mark J Daly; Andre Franke; Miles Parkes; Severine Vermeire; Jeffrey C Barrett; Judy H Cho Journal: Nature Date: 2012-11-01 Impact factor: 49.962
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