Analysis of the contribution of HLA genes to genetic predisposition in inflammatory bowel disease.
Crohn disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBDs) of unknown etiology. First-degree relatives of IBD patients have a 10-fold increase in risk of developing the same disease, and distinct associations between specific HLA types and both CD and UC have been reported. We have evaluated the contribution of genes at the HLA locus to susceptibility in IBD by linkage analysis of highly informative microsatellite polymorphisms in 43 families with multiple affected cases. No evidence for linkage of HLA to IBD was obtained under any of the four models tested. Analysis of HLA haplotype sharing in affected relatives indicated that the relative risk to a sibling conferred by the HLA locus was 1.11 in UC and 0.75 in CD, with upper (95%) confidence limits of 2.41 and 1.37, respectively. This suggests that other genetic or environmental factors are responsible for most of the familial aggregation in IBD.
Naom
I
I
Division of Medical and Molecular Genetics UMDS, Guy's Hospital, London, UK.
Lee
J
J
Ford
D
D
Bowman
S J
SJ
Lanchbury
J S
JS
Haris
I
I
Hodgson
S V
SV
Easton
D
D
Lennard-Jones
J
J
Mathew
C G
CG
D003093:Colitis, Ulcerative / Q000235:genetics; D003424:Crohn Disease / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D006680:HLA Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D008126:Lod Score; D008285:Major Histocompatibility Complex; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree; D012307:Risk Factors
D006680:HLA Antigens