Association of a CXCL9 polymorphism with pediatric Crohn's disease.
Genetic and environmental factors contribute to the etiopathogenesis of Crohn's disease (CD) and ulcerative colitis (UC). To identify new susceptibility genes, we determined the mRNA expression level of 88 genes from different biological contexts on colonic biopsies of CD and UC patients. We show that CXCL9 was overexpressed in colonic tissue of 3/5 CD and 3/3 UC patients compared to healthy controls. SNP genotyping for the 77147452G-->A polymorphism of the CXCL9 gene on 114 pediatric IBD patients and 120 ethnically matched unaffected adults detected a minor allele frequency of 20.3% in CD patients compared to 31.3% in controls (p=0.016). Strikingly, children with homozygosity for the wild-type allele had a significant earlier onset of CD than heterozygous individuals (11.1 versus 13.8 years). This is the first report of inverse association of the CXCL9 77147452G-->A polymorphism with pediatric CD. Our data may contribute to a better understanding of the pathophysiology underlying CD.
Lacher
Martin
M
Dr. von Haunersches Kinderspital, Pediatric Surgical Clinic, Research Laboratories, Ludwig-Maximilians-University of Munich, Lindwurmstr 4, D-80337 Munich, Germany. martin.lacher@lmu.de
Kappler
Roland
R
Berkholz
Stefan
S
Baurecht
Hansjoerg
H
von Schweinitz
Dietrich
D
Koletzko
Sibylle
S
D000293:Adolescent; D000328:Adult; D054370:Chemokine CXCL9 / Q000235:genetics*; D002648:Child; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000473:pathology; D003424:Crohn Disease / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000473:pathology; D008297:Male; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction
C080810:CXCL9 protein, human; D054370:Chemokine CXCL9