title: Lack of association of NKX2-3, IRGM, and ATG16L1 inflammatory bowel disease susceptibility variants with celiac disease.
abstract: Evidence about the presence of susceptibility factors shared among different autoimmune diseases is increasing. Based on this idea, NKX2-3, ATG16L1, and IRGM which are well-established inflammatory bowel disease risk factors, could be new celiac disease (CD) candidate genes. NKX2-3 encodes a transcription factor that in mice seems to be involved in gut development. The ATG16L1 and IRGM genes act in autophagy, a process related to innate and adaptive immunity. We aimed to study the implication of five polymorphisms in these genes in CD susceptibility: rs10883365 and rs888208 in the NKX2-3 gene, rs2241880 in ATG16L1, and rs10065172 and rs4958847 in IRGM. Association studies were performed using 725 Spanish CD patients and 956 ethnically matched healthy controls, as well as 309 parent-child trios. Genetic frequencies were compared with the chi(2) test and the familial study used the transmission disequilibrium test. Differences between CD patients and controls did not reach significance when genotypic and allelic frequencies were compared. No differential transmission of alleles or haplotypes from heterozygous parents to affected children was observed in the familial study. In conclusion, no evidence of association with CD has been reported for the Crohn's disease susceptibility polymorphisms studied in the NKX2-3, ATG16L1, and IRGM genes.
authors.affiliation: Clinical Immunology Department, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Dema
authors.forename: Miguel
authors.initials: M
authors.lastname: Fernández-Arquero
authors.forename: Carlos
authors.initials: C
authors.lastname: Maluenda
authors.forename: Isabel
authors.initials: I
authors.lastname: Polanco
authors.forename: M Angeles
authors.initials: MA
authors.lastname: Figueredo
authors.forename: Emilio G
authors.initials: EG
authors.lastname: de la Concha
authors.forename: Elena
authors.initials: E
authors.lastname: Urcelay
authors.forename: Concepción
authors.initials: C
authors.lastname: Núñez
mesh_terms: D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000235:genetics* / Q000276:immunology; D002446:Celiac Disease / Q000150:complications / Q000235:genetics* / Q000276:immunology; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000276:immunology; D020022:Genetic Predisposition to Disease; D018398:Homeodomain Proteins / Q000235:genetics* / Q000276:immunology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics* / Q000276:immunology
chemical_list: C518959:ATG16L1 protein, human; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D018398:Homeodomain Proteins; C534957:NKX2-3 protein, human; D014157:Transcription Factors; D019204:GTP-Binding Proteins; C513539:IRGM protein, human