title: The role of inflammatory bowel disease susceptibility loci in multiple sclerosis and systemic lupus erythematosus.
abstract: To date, three loci have been validated to confer susceptibility to inflammatory bowel disease (IBD): the CARD15/NOD2 gene, the discs large homolog 5 gene (DLG5), and the IBD5 locus on 5q31 (IBD5). We have explored the possibility that these loci may also be associated with susceptibility to two other chronic inflammatory diseases, multiple sclerosis (MS) and systemic lupus erythematosus (SLE). As the CARD15 risk alleles had previously been assessed in our collection of 496 MS trios, we focused our efforts on the DLG5 risk allele and the IBD5(risk) haplotype (IBD5(risk)) for MS. While there is no evidence of association within our MS sample with either of these polymorphisms, screening of 1027 subjects with SLE suggests that IBD5(risk) may have a modest contribution to disease risk in the subset of SLE subjects without lupus nephritis. In addition, a pooled analysis of existing published and unpublished data in 1305 cases of SLE genotyped for the CARD15 risk alleles suggests that only the CARD15(908R) IBD risk allele may have a strong effect on risk of SLE. Our data, therefore, suggest that both the CARD15 gene and the IBD5 locus may have a role as general susceptibility loci for certain common, genetically complex inflammatory diseases.
authors.affiliation: Center for Neurologic Diseases, Department of Neurology, Harvard Medical School and Brigham and Women's Hospital, MA, USA.
authors.forename: P L
authors.initials: PL
authors.lastname: De Jager
authors.forename: R
authors.initials: R
authors.lastname: Graham
authors.forename: L
authors.initials: L
authors.lastname: Farwell
authors.forename: S
authors.initials: S
authors.lastname: Sawcer
authors.forename: A
authors.initials: A
authors.lastname: Richardson
authors.forename: T W
authors.initials: TW
authors.lastname: Behrens
authors.forename: A
authors.initials: A
authors.lastname: Compston
authors.forename: D A
authors.initials: DA
authors.lastname: Hafler
authors.forename: J
authors.initials: J
authors.lastname: Kere
authors.forename: T J
authors.initials: TJ
authors.lastname: Vyse
authors.forename: J D
authors.initials: JD
authors.lastname: Rioux
mesh_terms: D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D005091:Exons / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D009103:Multiple Sclerosis / Q000235:genetics*; D053473:Nod2 Signaling Adaptor Protein; D020641:Polymorphism, Single Nucleotide; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C114461:DLG5 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D025521:Tumor Suppressor Proteins