Evidence for genetic heterogeneity in inflammatory bowel disease (IBD); HLA genes in the predisposition to suffer from ulcerative colitis (UC) and Crohn's disease (CD).
Family and epidemiological studies support a genetic susceptibility to UC and CD. Conflicting reports regarding associations between UC and HLA-DR2 and between CD and various HLA alleles have been published. The aim of this study was to determine whether molecularly defined HLA-DR genes are associated with these diseases in a Dutch group of patients. Fifty-nine unrelated Dutch UC patients and 89 CD patients were typed using DNA-based methods. A total of 2400 healthy local blood donors served as controls. The phenotype frequency of the HLA-DRB1*15 allele was increased in UC patients compared with controls (42% versus 26% in controls; P = 0.006; odds ratio (OR) = 2.1), and was predominantly found in female patients (53% versus 24%; P = 0.001; OR = 3.5). The DRB1*15 allele was increased in UC patients having a positive family history (P = 0.01; OR = 5.8). Among the 16 patients who showed an increase in extent of disease during follow up, 10 were DRB1*15+ (P = 0.002; OR = 4.8). The frequency of the DRB1*13 allele was decreased in patients with UC (15% versus 28% in controls; P = 0.04; OR = 0.5). In CD, no association was observed between disease or particular clinical subgroups and any allele tested. The present study provides additional evidence for the genetic association between UC and HLA-DRB1*15, and supports recent findings that the susceptibility gene(s) for CD is not located in the HLA class II region.
Bouma
G
G
Department of Gastroenterology, Academic Hospital Vrije Universiteit Amsterdam, The Netherlands.
Oudkerk Pool
M
M
Crusius
J B
JB
Schreuder
G M
GM
Hellemans
H P
HP
Meijer
B U
BU
Kostense
P J
PJ
Giphart
M J
MJ
Meuwissen
S G
SG
Peña
A S
AS
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D002648:Child; D003093:Colitis, Ulcerative / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D003424:Crohn Disease / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D004247:DNA / Q000032:analysis; D005260:Female; D006684:HLA-DR Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D016133:Polymerase Chain Reaction; D015995:Prevalence; D012737:Sex Factors
D006684:HLA-DR Antigens; D004247:DNA