Open AccessDistinct and overlapping genetic loci in crohn's disease and ulcerative colitis: Correlations with pathogenesis
Author(s) -
Waterman Matti,
Xu Wei,
Stempak Joanne M.,
Milgrom Raquel,
Bernstein Charles N.,
Griffiths Anne M.,
Greenberg Gordon R.,
Steinhart A. Hillary,
Silverberg Mark S.
Publication year - 2011
Publication title -
inflammatory bowel diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.932
H-Index - 146
eISSN - 1536-4844
pISSN - 1078-0998
DOI - 10.1002/ibd.21579
Subject(s) - single nucleotide polymorphism , ptpn22 , ulcerative colitis , genotype , allele , inflammatory bowel disease , nod2 , crohn's disease , pathogenesis , biology , allele frequency , genotype frequency , immunology , genetics , medicine , disease , gene
Background: A common genotypic basis for ulcerative colitis (UC) and Crohn's disease (CD) is implied by overlapping clinical characteristics, epidemiological studies, and association of genes with both UC and CD. We evaluated the overlap between CD and UC genetic loci stratified by pathogenetic pathways and by disease location. Methods: The allele frequencies of six UC‐associated and 34 CD‐associated single nucleotide polymorphisms (SNPs) were determined in a Canadian IBD cohort ( n = 2374). Differences between CD, UC, colon‐only CD, ileal CD, and controls were analyzed controlling for ethnicity, age of diagnosis, and gender. Results: In all, 21 of 34 CD‐associated SNPs had similar allele frequencies in UC ( n = 1230) and CD ( n = 1144). Three of six UC‐associated SNPs had significantly different frequencies in CD ( n = 1144). Most of the divergence in allele frequency among CD and UC was noted in NOD2/autophagy pathway SNPs, while most SNPs with similar frequencies were in IL‐22/23 Th17, adaptive immunity, and barrier pathways. Colon‐only CD ( n = 228) was compared with healthy controls: three of six UC SNPs (in MST1, HLA‐DRA , and IL‐23R ) and 11 of 34 CD SNPs: in IRGM, NOD2 (rs2066845), CCNY, MST1, IL23R, PTPN22, C11orf30, ZNF365, PTPN2, PSMG1 , and rs1456893 were significantly associated. In all, 29 of 34 CD SNPs had similar allele frequencies in colonic CD compared with ileal CD ( n = 366). All UC SNPs had similar frequencies in UC and colonic CD. Conclusions: Our results suggest that CD and UC share common genetic associations related to impaired adaptive immunity and diverge in pathways of foreign antigen processing. Colon‐only CD overlaps extensively with UC and considerably with ileal CD. (Inflamm Bowel Dis 2010)