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CD40: Novel Association with Crohn's Disease and Replication in Multiple Sclerosis Susceptibility
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Blanco-Kelly, Fiona; Matesanz, Fuencisla; Alcina, Antonio; Teruel, María; Díaz-Gallo, Lina M.; Gómez-García, María; López-Nevot, Miguel A.; +10 Authors
Blanco-Kelly, Fiona; Matesanz, Fuencisla; Alcina, Antonio; Teruel, María; Díaz-Gallo, Lina M.; Gómez-García, María; López-Nevot, Miguel A.; Rodrigo, Luis; Nieto, Antonio; Cardeña, Carlos; Alcain, Guillermo; Díaz-Rubio, Manuel; G. de la Concha, Emilio; Fernandez, Oscar; Arroyo, Rafael; Martín, Javier; Urcelay, Elena;
CD40: Novel Association with Crohn's Disease and Replication in Multiple Sclerosis Susceptibility
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.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.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)].The impact of CD40 rs1883832 on MS and CD risk points to a common signaling shared by these autoimmune conditions.
Adult, Multiple Sclerosis, Medical Subject Headings::Diseases::Immune System Diseases::Autoimmune Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis, Genotype, Science, Medical Subject Headings::Diseases::Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Inflammatory Bowel Diseases::Crohn Disease, Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic, Gene, Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans, Young Adult, Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genotype, Crohn Disease, Gene Frequency, Medical Subject Headings::Named Groups::Persons::Age Groups::Adult, Humans, Genetic Predisposition to Disease, Polymorphism, CD40 Antigens, Encephalomyelitis, Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Alleles, Alleles, Polymorphism, Genetic, Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Susceptibility::Genetic Predisposition to Disease, Medical Subject Headings::Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Antigens, Differentiation::Antigens, CD::Antigens, CD40, Q, R, Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Gene Frequency, Medical Subject Headings::Diseases::Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Colonic Diseases::Colitis::Colitis, Ulcerative, Medicine, Colitis, Ulcerative, Single-Nucleotide, Research Article
Adult, Multiple Sclerosis, Medical Subject Headings::Diseases::Immune System Diseases::Autoimmune Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis, Genotype, Science, Medical Subject Headings::Diseases::Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Inflammatory Bowel Diseases::Crohn Disease, Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic, Gene, Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans, Young Adult, Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genotype, Crohn Disease, Gene Frequency, Medical Subject Headings::Named Groups::Persons::Age Groups::Adult, Humans, Genetic Predisposition to Disease, Polymorphism, CD40 Antigens, Encephalomyelitis, Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Alleles, Alleles, Polymorphism, Genetic, Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Susceptibility::Genetic Predisposition to Disease, Medical Subject Headings::Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Antigens, Differentiation::Antigens, CD::Antigens, CD40, Q, R, Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Gene Frequency, Medical Subject Headings::Diseases::Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Colonic Diseases::Colitis::Colitis, Ulcerative, Medicine, Colitis, Ulcerative, Single-Nucleotide, Research Article
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).62 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10% views 76 downloads 100 - 76views100downloads
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This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
Citations provided by BIP!popularityPopularity provided by BIP!
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
Popularity provided by BIP!influenceInfluence provided by BIP!
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
Influence provided by BIP!impulseImpulse provided by BIP!
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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