Polymorphism of the IRGM gene might predispose to fistulizing behavior in Crohn's disease.
OBJECTIVE
Recently, genome-wide association analyses have identified single nucleotide polymorphisms in the IRGM gene (rs1000113 and rs4958847) as strong candidate susceptibility factors for Crohn's disease (CD). The aim of our study was to test whether these variants are associated with inflammatory bowel disease (IBD) in adult- and childhood-onset Italian patients.


METHODS
Allele and genotype frequencies of rs1000113 and rs4958847 were determined in 823 CD (265 younger than 19 years at diagnosis), 353 ulcerative colitis (UC) (130 younger than 19 years at diagnosis), and 578 controls. Genotype distributions were examined both within IBD clinical sub-phenotypes and CARD15 genotypes.


RESULTS
rs1000113 and rs4958847 were both associated with adult-onset (P=2 x 10(-4); P=2.5 x 10(-3), respectively) and childhood-onset (P=4 x 10(-4); P=8 x 10(-3), respectively) CD cohorts. Similarly, the genotype frequencies remained significantly different for both variants (adult rs1000113, P=1 x 10(-4); rs4958847, P=1 x 10(-3); pediatric rs1000113, P=2.3 x 10(-4); rs4958847, P=9.6 x 10(-3)). At logistic regression, the rs4958847 polymorphism was associated with fistulizing behavior (P=0.037, OR=1.54, CI=1.02-2.31) and perianal fistulas (P=0.045, OR=1.55, CI=1.01-2.38). Conversely, no association with UC and sub-phenotypes was shown.


CONCLUSIONS
We replicated the previously reported associations between CD and rs1000113 and rs4958847, confirming that IRGM is a susceptibility locus only for CD, either adult- or early-onset in the Italian population; furthermore, we have also shown its influence on specific clinical features (fistulizing disease).
Latiano
A
A
Unit of Gastroenterology and Endoscopy, IRCCS, Casa Sollievo della Sofferenza Hospital, Viale Cappuccini 1, San Giovanni Rotondo, Italy.
Palmieri
O
O
Cucchiara
S
S
Castro
M
M
D'Incà
R
R
Guariso
G
G
Dallapiccola
B
B
Valvano
M R
MR
Latiano
T
T
Andriulli
A
A
Annese
V
V
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D003424:Crohn Disease / Q000150:complications / Q000235:genetics*; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012003:Rectal Fistula / Q000150:complications / Q000235:genetics*; D055815:Young Adult
D019204:GTP-Binding Proteins; C513539:IRGM protein, human