IL-10 and TNF-alpha promoter haplotypes are associated with childhood Crohn's disease location.
OBJECTIVE
To determine the distribution and frequencies of the genotypes and haplotypes of the genes encoding for the glucocorticoid receptor (GR), the tumor necrosis factor (TNF)-alpha and the interleukin (IL)-10 in childhood Crohn's disease (CD) and to assess the impact of the corresponding DNA variants on clinical and disease phenotypes.


METHODS
Ten variants in GR, TNF-alpha and IL-10 were genotyped in 113 childhood CD cases and 95 healthy subjects, both of French-Canadian origin.


RESULTS
For the GR polymorphisms (R23K and N363S) and IL-10 variants in the 5'flanking region (-1082 G > A, -819 T > C and -592 A > C), no difference was observed in allele and genotype frequencies between CD patients and controls. At the haplotype level, we found three IL-10 haplotypes previously described in Caucasians (GCC, ACC and ATA) and three novel haplotypes only present in IBD patients. When we analyzed the haplotype distribution with the anatomical location of the disease, the GCC haplotype was associated with the colonic and the ACC haplotype with the terminal ileum location, respectively. The genotyping of five polymorphisms in the promoter region of the TNF-alpha gene (-1031 T > C, -863 A > C, -857 T > C, -308 A > G and -238 A > G) revealed a significant overrepresentation of homozygous -1031 CC among CD patients (OR = 9.9) and an association with the colonic location. For TNF-alpha, eleven haplotypes were inferred, including two frequent ones, TCCGG and CACGG, which were significantly observed more frequently in controls and cases, respectively.


CONCLUSIONS
This is one of the first studies investigating the association between haplotype structure and disease location in a CD pediatric cohort. Our results will help to increase our understanding of the genetic determinants of childhood CD.
Sanchez
Rocio
R
Research Center, Sainte-Justine University Health Center, Montreal H3T 1C5, Canada.
Levy
Emile
E
Costea
Florin
F
Sinnett
Daniel
D
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology; D015810:Linkage Disequilibrium; D008297:Male; D011401:Promoter Regions, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000276:immunology; D055815:Young Adult
D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10