PADI4 genotype is not associated with rheumatoid arthritis in a large UK Caucasian population.
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).


CONCLUSIONS
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.
Burr
Marian L
ML
arc-Epidemiology Unit, University of Manchester, Oxford Road, Manchester, UK.
Naseem
Haris
H
Hinks
Anne
A
Eyre
Steve
S
Gibbons
Laura J
LJ
Bowes
John
J
Wilson
Anthony G
AG
Maxwell
James
J
Morgan
Ann W
AW
Emery
Paul
P
Steer
Sophia
S
Hocking
Lynne
L
Reid
David M
DM
Wordsworth
Paul
P
Harrison
Pille
P
Thomson
Wendy
W
Worthington
Jane
J
Barton
Anne
A
D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology; D001323:Autoantibodies / Q000032:analysis; D004812:Epidemiologic Methods; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006867:Hydrolases / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases; D044465:White People / Q000235:genetics
D001323:Autoantibodies; D006867:Hydrolases; C000629235:PADI4 protein, human; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases