PADI4 genotype is not associated with rheumatoid arthritis in a large UK Caucasian population
Open Access
- 25 May 2009
- journal article
- research article
- Published by BMJ in Annals Of The Rheumatic Diseases
- Vol. 69 (4), 666-670
- https://doi.org/10.1136/ard.2009.111294
Abstract
Background 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. Methods 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. Results 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). Conclusion 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.Keywords
This publication has 26 references indexed in Scilit:
- A Functional Haplotype of PADI4 Gene in Rheumatoid Arthritis: Positive Correlation in a French PopulationThe Journal of Rheumatology, 2009
- Investigation of polymorphisms in the PADI4 gene in determining severity of inflammatory polyarthritisAnnals Of The Rheumatic Diseases, 2005
- PADI4 polymorphisms are not associated with rheumatoid arthritis in the Spanish populationRheumatology, 2005
- Calculating measures of biological interactionEuropean Journal of Epidemiology, 2005
- Genetic and genomic studies of PADI4 in rheumatoid arthritisRheumatology, 2005
- 'Racial' differences in genetic effects for complex diseasesNature Genetics, 2004
- A functional haplotype of the PADI4 gene associated with rheumatoid arthritis in a Japanese population is not associated in a United Kingdom populationArthritis & Rheumatism, 2004
- Cutting Edge: The Conversion of Arginine to Citrulline Allows for a High-Affinity Peptide Interaction with the Rheumatoid Arthritis-Associated HLA-DRB1*0401 MHC Class II MoleculeThe Journal of Immunology, 2003
- Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritisNature Genetics, 2003
- Characterizing the quantitative genetic contribution to rheumatoid arthritis using data from twinsArthritis & Rheumatism, 2000