Inflammatory bowel disease is linked to 19p13 and associated with ICAM-1.
Genome-wide scans have implicated several susceptibility loci, but linkage of 19p13 (IBD6) to Crohn's disease (CD) has not been fully replicated. We report a replication study of IBD6 in a UK Caucasian population. Two hundred eighty-four affected sibling pairs from 234 families were used for the linkage study. Linkage between IBD6 linkage and CD was replicated (LOD score = 1.59). Two candidate genes (DDXL and ICAM-1) within the IBD6 locus were examined in a case/control study with a total of 228 CD and 243 ulcerative colitis (UC) patients and 407 healthy controls. No association to either UC or CD was found in three novel intronic single nucleotide polymorphisms (SNPs) in DDXL. For ICAM-1, a significant association was found between K469 homozygosity and CD overall (39.9% vs 29.4%; Pc = 0.0096) and between E469 and fistulating disease (21.8% vs 10.0%, Pc = 0.030). In the UC group, limited disease extent was associated with homozygosity of the G241 allele (82.7% vs 64.7%, Pc = 0.0040). These data support linkage for CD at 19p13 and suggest that the amino acid polymorphisms in ICAM-1 may be associated with IBD.
Gastroenterology Unit, Gibson Laboratories, Radcliffe Infirmary, University of Oxford, Oxford, UK.
Jin Hong
JH
Low
Fiona A
FA
Williams
Xuesong
X
Yang
Sue
S
Cullen
James
J
Colley
Khoon Lin
KL
Ling
Alessandro
A
Armuzzi
Tariq
T
Ahmad
Matt J
MJ
Neville
Bryan M
BM
Dechairo
Robert
R
Walton
Nick J
NJ
Lench
Derek P
DP
Jewell
D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002888:Chromosomes, Human, Pair 19; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000276:immunology; D003424:Crohn Disease / Q000235:genetics* / Q000276:immunology; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006720:Homozygote; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D011110:Polymorphism, Genetic; D035781:Siblings; D044465:White People / Q000235:genetics*
D018799:Intercellular Adhesion Molecule-1