Polymorphisms in interleukin-10 gene according to mutations of NOD2/CARD15 gene and relation to phenotype in Spanish patients with Crohn's disease.
OBJECTIVE
To examine the contribution of interleukin-10 (IL-10) gene polymorphisms to Crohnos disease (CD) phenotype, and the possible genetic epistasis between IL-10 gene polymorphisms and CARD15/NOD2 gene mutations.


METHODS
A cohort of 205 Spanish unrelated patients with Crohn's disease recruited from a single center was studied. All patients were rigorously phenotyped and followed-up for at least 3 years (mean time, 12.5 years). The clinical phenotype was established prior to genotyping.


RESULTS
The correlation of genotype-Vienna classification groups showed that the ileocolonic location was significantly associated with the -1082G allele in the NOD2/CARD15 mutation-positive patients (RR=1.52, 95%CI, 1.21 to 1.91, P=0.008). The multivariate analysis demonstrated that the IL-10 G14 microsatellite allele in the NOD2/CARD15 mutation positive patients was associated with two risk factors, history of appendectomy (RR=2.15, 95%CI=1.1-4.30, P=0.001) and smoking habit at diagnosis (RR=1.29, 95%CI=1.04-4.3, P=0.04).


CONCLUSIONS
In Spanish population from Madrid, in CD patients carrying at least one NOD2/CARD15 mutation, the -1082G allele is associated with ileocolonic disease and the IL-10G14 microsatellite allele is associated with previous history of appendectomy and smoking habit at diagnosis. These data provide further molecular evidence for a genetic basis of the clinical heterogeneity of CD.
Department of Gastroenterology, Hospital Clínico San Carlos de Madrid, Universidad Complutense, Madrid, Spain. jmendozah@meditex.es
Juan L
JL
Mendoza
Elena
E
Urcelay
Raquel
R
Lana
Alfonso
A
Martinez
Carlos
C
Taxonera
Emilio G
EG
de la Concha
Manuel
M
Díaz-Rubio
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D003424:Crohn Disease / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein; D010641:Phenotype; D011110:Polymorphism, Genetic; D013030:Spain
D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D016753:Interleukin-10