P G Bronson1, L A Criswell, L F Barcellos. 1. Division of Epidemiology, School of Public Health, University of California, 209 Hildebrand Hall, Berkeley, CA 94720, USA.
Abstract
BACKGROUND: An association between major histocompatibility complex (MHC) genes, particularly those within the class II HLA region, and rheumatoid arthritis (RA) is well established, and accounts for an estimated 30% of the genetic component in RA. The MHC class II transactivator gene (MHC2TA) on chromosome 16p13 has recently emerged as the most important transcription factor regulating genes required for class II MHC-restricted antigen presentation. Previous studies of a promoter region polymorphism (-168A/G, rs3087456) in the MHC2TA gene and RA have yielded conflicting results. OBJECTIVE: To assess the association of the MHC2TA -168A/G polymorphism (rs3087456) and risk for RA by meta-analysis. METHODS: Meta-analysis was performed for 6861 patients with RA and 9270 controls from 10 case-control studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each study. Summary ORs and 95% CIs were calculated for random effects models. RESULTS: No effect was observed for the G risk allele (OR 1.02, 95% CI 0.93 to 1.12, p = 0.70) or the GG risk genotype (OR 1.14, 95% CI 0.95 to 1.36, p = 0.16). CONCLUSIONS: Our results indicate that the MHC2TA -168A/G polymorphism (rs3087456) is not associated with RA yet underscore the importance of including shared epitope allele carrier status, secondary phenotypes and more complete characterisation of MHC2TA variation in future studies.
BACKGROUND: An association between major histocompatibility complex (MHC) genes, particularly those within the class II HLA region, and rheumatoid arthritis (RA) is well established, and accounts for an estimated 30% of the genetic component in RA. The MHC class II transactivator gene (MHC2TA) on chromosome 16p13 has recently emerged as the most important transcription factor regulating genes required for class II MHC-restricted antigen presentation. Previous studies of a promoter region polymorphism (-168A/G, rs3087456) in the MHC2TA gene and RA have yielded conflicting results. OBJECTIVE: To assess the association of the MHC2TA-168A/G polymorphism (rs3087456) and risk for RA by meta-analysis. METHODS: Meta-analysis was performed for 6861 patients with RA and 9270 controls from 10 case-control studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each study. Summary ORs and 95% CIs were calculated for random effects models. RESULTS: No effect was observed for the G risk allele (OR 1.02, 95% CI 0.93 to 1.12, p = 0.70) or the GG risk genotype (OR 1.14, 95% CI 0.95 to 1.36, p = 0.16). CONCLUSIONS: Our results indicate that the MHC2TA-168A/G polymorphism (rs3087456) is not associated with RA yet underscore the importance of including shared epitope allele carrier status, secondary phenotypes and more complete characterisation of MHC2TA variation in future studies.
Authors: S T Sherry; M H Ward; M Kholodov; J Baker; L Phan; E M Smigielski; K Sirotkin Journal: Nucleic Acids Res Date: 2001-01-01 Impact factor: 16.971
Authors: Stephen Eyre; Anne Barton; Neil Shephard; Anne Hinks; William Brintnell; Kirsten MacKay; Alan Silman; William Ollier; Paul Wordsworth; Sally John; Jane Worthington Journal: Arthritis Rheum Date: 2004-03
Authors: Alfonso Martínez; Marta Sánchez-Lopez; Jezabel Varadé; Ana Mas; M Carmen Martín; Virginia de Las Heras; Rafael Arroyo; Juan Luis Mendoza; Manuel Díaz-Rubio; Benjamín Fernández-Gutiérrez; Emilio G de la Concha; Elena Urcelay Journal: Ann Rheum Dis Date: 2006-09-29 Impact factor: 19.103
Authors: Maria Swanberg; Olle Lidman; Leonid Padyukov; Per Eriksson; Eva Akesson; Maja Jagodic; Anna Lobell; Mohsen Khademi; Ola Börjesson; Cecilia M Lindgren; Pia Lundman; Anthony J Brookes; Juha Kere; Holger Luthman; Lars Alfredsson; Jan Hillert; Lars Klareskog; Anders Hamsten; Fredrik Piehl; Tomas Olsson Journal: Nat Genet Date: 2005-04-10 Impact factor: 38.330
Authors: Damini Jawaheer; Wentian Li; Robert R Graham; Wei Chen; Aarti Damle; Xiangli Xiao; Joanita Monteiro; Houman Khalili; Annette Lee; Robert Lundsten; Ann Begovich; Teodorica Bugawan; Henry Erlich; James T Elder; Lindsey A Criswell; Michael F Seldin; Christopher I Amos; Timothy W Behrens; Peter K Gregersen Journal: Am J Hum Genet Date: 2002-08-09 Impact factor: 11.025
Authors: Sherine E Gabriel; Cynthia S Crowson; Hilal Maradit Kremers; Michele F Doran; Carl Turesson; W Michael O'Fallon; Eric L Matteson Journal: Arthritis Rheum Date: 2003-01
Authors: P G Bronson; B A Goldstein; P P Ramsay; K B Beckman; J A Noble; J A Lane; M F Seldin; J A Kelly; J B Harley; K L Moser; P M Gaffney; T W Behrens; L A Criswell; L F Barcellos Journal: Genes Immun Date: 2011-05-26 Impact factor: 2.676
Authors: Paola G Bronson; Stacy Caillier; Patricia P Ramsay; Jacob L McCauley; Rebecca L Zuvich; Philip L De Jager; John D Rioux; Adrian J Ivinson; Alastair Compston; David A Hafler; Stephen J Sawcer; Margaret A Pericak-Vance; Jonathan L Haines; Stephen L Hauser; Jorge R Oksenberg; Lisa F Barcellos Journal: Hum Mol Genet Date: 2010-03-08 Impact factor: 6.150
Authors: J F Mendoza Rincón; A K Rodríguez Elias; J M Fragoso; G Vargas Alarcón; K Maldonado Murillo; M L Rivas Jiménez; R E Barbosa Cobos; S Jimenez Morales; G Lugo Zamudio; C Tovilla Zárate; J Ramírez Bello Journal: Rheumatol Int Date: 2015-09-08 Impact factor: 2.631
Authors: Marcus Ronninger; Maria Seddighzadeh; Morten Christoph Eike; Darren Plant; Nina A Daha; Beate Skinningsrud; Jane Worthington; Tore K Kvien; Rene E M Toes; Benedicte A Lie; Lars Alfredsson; Leonid Padyukov Journal: PLoS One Date: 2012-03-26 Impact factor: 3.240