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Polymorphisms of the peptidylarginine deiminase type 4 (PADI4) gene confer susceptibility to rheumatoid arthritis (RA) in East Asian people. However, studies in European populations have produced conflicting results. This study explored the association of the PADI4 genotype with RA in a large UK Caucasian population.The PADI4_94 (rs2240340) single nucleotide polymorphism (SNP) was directly genotyped in a cohort of unrelated UK Caucasian patients with RA (n=3732) and population controls (n=3039). Imputed data from the Wellcome Trust Case Control Consortium (WTCCC) was used to investigate the association of PADI4_94 with RA in an independent group of RA cases (n=1859) and controls (n=10 599). A further 56 SNPs spanning the PADI4 gene were investigated for association with RA using data from the WTCCC study.The PADI4_94 genotype was not associated with RA in either the present cohort or the WTCCC cohort. Combined analysis of all the cases of RA (n=5591) and controls (n=13 638) gave an overall OR of 1.01 (95% CI 0.96 to 1.05, p=0.72). No association with anti-CCP antibodies and no interaction with either shared epitope or PTPN22 was detected. No evidence for association with RA was identified for any of the PADI4 SNPs investigated. Meta-analysis of previously published studies and our data confirmed no significant association between the PADI4_94 genotype and RA in people of European descent (OR 1.06, 95% CI 0.99 to 1.13, p=0.12).In the largest study performed to date, the PADI4 genotype was not a significant risk factor for RA in people of European ancestry, in contrast to Asian populations.

Original publication

DOI

10.1136/ard.2009.111294

Type

Journal article

Journal

Annals of the rheumatic diseases

Publication Date

04/2010

Volume

69

Pages

666 - 670

Addresses

arc-Epidemiology Unit, University of Manchester, Oxford Road, Manchester, UK.

Keywords

BIRAC Consortium, YEAR Consortium, Humans, Arthritis, Rheumatoid, Genetic Predisposition to Disease, Hydrolases, Autoantibodies, Epidemiologic Methods, Gene Frequency, Genotype, Polymorphism, Single Nucleotide, European Continental Ancestry Group, Female, Male