Association of FcgR2a, but not FcgR3a, with inflammatory bowel diseases across three Caucasian populations.
BACKGROUND
The Fc receptors II and III (FcgR2a, and FcgR3a) play a crucial role in the regulation of the immune response. The FcgR2a*519GG and FcgR3a*559CC genotypes have been associated with several autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, nephritis, and possibly to type I diabetes, and celiac disease. In a large multicenter, two-stage study of 6570 people, we tested whether the FcgR2a and FcgR3a genes were also involved in inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC).


METHODS
We genotyped the FcgR2a*A519G and FcgR3a*A559C functional variants in 4205 IBD patients in six well-phenotyped Caucasian IBD cohorts and 2365 ethnically matched controls recruited from the Netherlands, Spain, and New Zealand.


RESULTS
In the initial Dutch study we found a significant association of FcgR2a genotypes with IBD (P-genotype = 0.02); while the FcgR2a*519GG was more common in controls (23%) than in IBD patients (18%; odds ratio [OR] = 0.75; 95% confidence interval [CI] 0.61-0.92; P = 0.004). This association was corroborated by a combined analysis across all the study populations (Mantel-Haenszel [MH] OR = 0.84; 0.74-0.95; P = 0.005) in the next stage. The Fcgr2a*GG genotype was associated with both UC (MH-OR = 0.84; 0.72-0.97; P = 0.01) and CD (MH-OR = 0.84; 0.73-0.97; P = 0.01), suggesting that this genotype confers a protective effect against IBD. There was no association of FcgR3a*A559C genotypes with IBD, CD, or UC in any of the three studied populations.


CONCLUSIONS
The FcgR2a*519G functional variant was associated with IBD and reduced susceptibility to UC and to CD in Caucasians. There was no association between FcgR3a*5A559C and IBD, CD or UC.
Weersma
Rinse K
RK
Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands.
Crusius
J Bart A
JB
Roberts
Rebecca L
RL
Koeleman
Bobby P C
BP
Palomino-Morales
Rogelio
R
Wolfkamp
Simone
S
Hollis-Moffatt
Jade E
JE
Festen
Eleonora A M
EA
Meisneris
Sander
S
Heijmans
Roel
R
Noble
Colin L
CL
Gearry
Richard B
RB
Barclay
Murrary L
ML
Gómez-Garcia
María
M
Lopez-Nevot
Miguel A
MA
Nieto
Antonio
A
Rodrigo
Luis
L
Radstake
Timothy R D J
TR
van Bodegraven
Adriaan A
AA
Wijmenga
Cisca
C
Merriman
Tony R
TR
Stokkers
Pieter C F
PC
Peña
A Salvador
AS
Martín
Javier
J
Alizadeh
Behrooz Z
BZ
D016022:Case-Control Studies; D015331:Cohort Studies; D003093:Colitis, Ulcerative / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D009426:Netherlands; D009520:New Zealand; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017452:Receptors, IgG / Q000235:genetics*; D013030:Spain; D044465:White People / Q000235:genetics*
C445323:FCGR2A protein, human; C496124:FCGR3A protein, human; D017452:Receptors, IgG