Contribution of IBD5 locus to clinical features of IBD patients.
OBJECTIVE
The aim of this study was to investigate the influence of the IBD5 locus on clinical features of inflammatory bowel disease (IBD) patients, and its possible interaction with the CARD15 gene.


METHODS
A cohort of 1,199 IBD patients (570 with CD and 629 with ulcerative colitis [UC]), and 357 healthy subjects were investigated. Information on clinical features was fully available for 855 IBD patients. Two SNPs in the IBD5 locus (IGR2198a_1 and IGR2096a_1) and the three major variants of CARD15 gene were genotyped in patients and controls.


RESULTS
Homozygous carriers of risk alleles were significantly more frequent in CD (22.6% for IGR2198a_1, OR = 1.6, p = 0.015; 21.9% for IGR2096a_1, OR = 1.6, p = 0.012) compared to controls (16.8% and 15.7%, respectively). The homozygote frequency was also increased in UC patients, but not significantly. No significant gene-gene interaction was detected between IBD5 and CARD15. A univariate analysis detected association between IBD5 and steno/fistulizing behavior in CD patients (OR = 1.9; p = 0.004), and presence of more extensive colitis in UC patients (OR = 1.7; p = 0.01). Results from multiple logistic regression, after correction for covariates, showed that the influence of IBD5 on clinical outcome of CD was completely masked by that of CARD15, while the influence on more extensive colitis in UC patients was confirmed.


CONCLUSIONS
Our study shows that presence of the IBD5 risk alleles, particularly in the homozygous state, is associated with IBD and especially with CD, without a significant epistasis with CARD15. The contribution of CARD15 risk alleles to CD clinical features is prominent on that of IBD5.
Latiano
Anna
A
Divisione di Gastroenterologia, Ospedale CSS-IRCCS, San Giovanni Rotondo, Italy.
Palmieri
O
O
Valvano
Rossella M
RM
D'Incà
Renata
R
Vecchi
Maurizio
M
Ferraris
Angelo
A
Sturniolo
Giacomo C
GC
Spina
Luisa
L
Lombardi
Giovanni
G
Dallapiccola
Bruno
B
Andriulli
Angelo
A
Devoto
Marcella
M
Annese
Vito
V
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D003093:Colitis, Ulcerative / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012307:Risk Factors
D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D004247:DNA