Evidence for inflammatory bowel disease of a susceptibility locus on the X chromosome

Gastroenterology. 2001 Mar;120(4):834-40. doi: 10.1053/gast.2001.22453.


Background & aims: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosome Mapping*
  • Female
  • Genetic Linkage
  • Genetic Predisposition to Disease*
  • Humans
  • Inflammatory Bowel Diseases / genetics*
  • Male
  • Microsatellite Repeats
  • X Chromosome / genetics*