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CD40: Novel Association with Crohn’s Disease and Replication in Multiple Sclerosis Susceptibility

AuthorsBlanco-Kelly, F.; Matesanz, F.; Alcina, Antonio; Teruel, María; Díaz-Gallo, L. M.; Gómez-García, María; López-Nevot, Miguel-Ángel; Rodrigo, Luis; Nieto, A.; Cardeña, C.; Alcain, G.; Díaz-Rubio, M.; de la Concha, Emilio G.; Fernández, Óscar; Arroyo, R.; Martín, J.; Urcelay, Elena
Issue Date12-Jul-2010
PublisherPublic Library of Science
AbstractBackground: A functional polymorphism located at 21 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. Methodology: 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. Principal Findings: 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)]. Conclusion: The impact of CD40 rs1883832 on MS and CD risk points to a common signaling shared by these autoimmune conditions.
Publisher version (URL)http://dx.doi.org/10.1371/journal.pone.0011520
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