Investigation of potential non-HLA rheumatoid arthritis susceptibility loci in a European cohort increases the evidence for nine markers.
BACKGROUND
Genetic factors have a substantial role in determining development of rheumatoid arthritis (RA), and are likely to account for 50-60% of disease susceptibility. Genome-wide association studies have identified non-human leucocyte antigen RA susceptibility loci which associate with RA with low-to-moderate risk.


OBJECTIVE
To investigate recently identified RA susceptibility markers using cohorts from six European countries, and perform a meta-analysis including previously published results.


METHODS
3311 DNA samples were collected from patients from six countries (UK, Germany, France, Greece, Sweden and Denmark). Genotype data or DNA samples for 3709 controls were collected from four countries (not Sweden or Denmark). Eighteen single nucleotide polymorphisms (SNPs) were genotyped using Sequenom MassArray technology. Samples with a >95% success rate and only those SNPs with a genotype success rate of >95% were included in the analysis. Scandinavian patient data were pooled and previously published Swedish control data were accessed as a comparison group. Meta-analysis was used to combine results from this study with all previously published data.


RESULTS
After quality control, 3209 patients and 3692 controls were included in the study. Eight markers (ie, rs1160542 (AFF3), rs1678542 (KIF5A), rs2476601 (PTPN22), rs3087243 (CTLA4), rs4810485 (CD40), rs5029937 (6q23), rs10760130 (TRAF1/C5) and rs7574865 (STAT4)) were significantly associated with RA by meta-analysis. All 18 markers were associated with RA when previously published studies were incorporated in the analysis. Data from this study increased the significance for association with RA and nine markers.


CONCLUSIONS
In a large European RA cohort further evidence for the association of 18 markers with RA development has been obtained.
Plant
Darren
D
arc-Epidemiology Unit, Stopford Building, The University of Manchester, Manchester M13 9PT, UK. darren.plant@manchester.ac.uk
Flynn
Edward
E
Mbarek
Hamdi
H
Dieudé
Philippe
P
Cornelis
François
F
Arlestig
Lisbeth
L
Dahlqvist
Solbritt Rantapää
SR
Goulielmos
George
G
Boumpas
Dimitrios T
DT
Sidiropoulos
Prodromos
P
Johansen
Julia S
JS
Ørnbjerg
Lykke M
LM
Hetland
Merete Lund
ML
Klareskog
Lars
L
Filer
Andrew
A
Buckley
Christopher D
CD
Raza
Karim
K
Witte
Torsten
T
Schmidt
Reinhold E
RE
Worthington
Jane
J
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
D005819:Genetic Markers