title: CD40: novel association with Crohn's disease and replication in multiple sclerosis susceptibility.
abstract: BACKGROUND
  A functional polymorphism located at -1 from the start codon of the CD40 gene, rs1883832, was previously reported to disrupt a Kozak sequence essential for translation. It has been consistently associated with Graves' disease risk in populations of different ethnicity and genetic proxies of this variant evaluated in genome-wide association studies have shown evidence of an effect in rheumatoid arthritis and multiple sclerosis (MS) susceptibility. However, the protective allele associated with Graves' disease or rheumatoid arthritis has shown a risk role in MS, an effect that we aimed to replicate in the present work. We hypothesized that this functional polymorphism might also show an association with other complex autoimmune condition such as inflammatory bowel disease, given the CD40 overexpression previously observed in Crohn's disease (CD) lesions.
  
  
  METHODS
  Genotyping of rs1883832C>T was performed in 1564 MS, 1102 CD and 969 ulcerative colitis (UC) Spanish patients and in 2948 ethnically matched controls by TaqMan chemistry.
  
  
  RESULTS
  The observed effect of the minor allele rs1883832T was replicated in our independent Spanish MS cohort [p = 0.025; OR (95% CI) = 1.12 (1.01-1.23)]. The frequency of the minor allele was also significantly higher in CD patients than in controls [p = 0.002; OR (95% CI) = 1.19 (1.06-1.33)]. This increased predisposition was not detected in UC patients [p = 0.5; OR (95% CI) = 1.04 (0.93-1.17)].
  
  
  CONCLUSIONS
  The impact of CD40 rs1883832 on MS and CD risk points to a common signaling shared by these autoimmune conditions.
authors.affiliation: Department of Clinical Immunology, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Fiona
authors.initials: F
authors.lastname: Blanco-Kelly
authors.forename: Fuencisla
authors.initials: F
authors.lastname: Matesanz
authors.forename: Antonio
authors.initials: A
authors.lastname: Alcina
authors.forename: María
authors.initials: M
authors.lastname: Teruel
authors.forename: Lina M
authors.initials: LM
authors.lastname: Díaz-Gallo
authors.forename: María
authors.initials: M
authors.lastname: Gómez-García
authors.forename: Miguel A
authors.initials: MA
authors.lastname: López-Nevot
authors.forename: Luis
authors.initials: L
authors.lastname: Rodrigo
authors.forename: Antonio
authors.initials: A
authors.lastname: Nieto
authors.forename: Carlos
authors.initials: C
authors.lastname: Cardeña
authors.forename: Guillermo
authors.initials: G
authors.lastname: Alcain
authors.forename: Manuel
authors.initials: M
authors.lastname: Díaz-Rubio
authors.forename: Emilio G
authors.initials: EG
authors.lastname: de la Concha
authors.forename: Oscar
authors.initials: O
authors.lastname: Fernandez
authors.forename: Rafael
authors.initials: R
authors.lastname: Arroyo
authors.forename: Javier
authors.initials: J
authors.lastname: Martín
authors.forename: Elena
authors.initials: E
authors.lastname: Urcelay
mesh_terms: D000328:Adult; D000483:Alleles; D019013:CD40 Antigens / Q000235:genetics*; D003093:Colitis, Ulcerative / Q000235:genetics; D003424:Crohn Disease / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D009103:Multiple Sclerosis / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D055815:Young Adult
chemical_list: D019013:CD40 Antigens