Evidence for inflammatory bowel disease of a susceptibility locus on the X chromosome.
OBJECTIVE
The technique of genomewide scanning has been applied successfully in inflammatory bowel disease (IBD). A number of putative susceptibility loci have been identified through genomewide searches including replicated regions of linkage on chromosomes 12, 16, 6 (the HLA region), and 14. We have investigated the contribution of the X chromosome in 145 Belgian affected relative pairs.


METHODS
In the first stage of the study, 79 (68 CD, 11 mixed) sibling pairs were genotyped at 12 microsatellite markers covering the X chromosome. In the second stage, 10 additional markers in the X-pericentromeric region were studied in the families involved in stage 1 together with 62 additional families (52 sibling pairs, 14 second-degree relative pairs).


RESULTS
In the first stage, evidence for linkage was found over a 30-cM pericentromeric region spanning dXs991, dXs990, and dXs8096 (multipoint maximum LOD score in the CD subgroup, 2.5; P = 0.0003). The remainder of the X chromosome was excluded (exclusion under LOD-2) for a locus with lambda(s) = 2. Fine mapping in the second stage confirmed linkage, and narrowed and shifted the linked region to Xq21.3 around dXs1203 (nonparametric linkage [NPL], 2.90; P = 0.0017). The NPL-1 interval around the linkage peak comprises 19.7 cM.


CONCLUSIONS
These data provide suggestive evidence for the presence and chromosomal location of an X-linked susceptibility gene in IBD.
Gastroenterology Unit, University Hospital Gasthuisberg, Leuven, Belgium.
S
S
Vermeire
J
J
Satsangi
M
M
Peeters
M
M
Parkes
D P
DP
Jewell
R
R
Vlietinck
P
P
Rutgeerts
D002874:Chromosome Mapping; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D014960:X Chromosome / Q000235:genetics*