title: Association of IL10 promoter polymorphisms with idiopathic achalasia.
abstract: Idiopathic achalasia is an esophageal motor disorder of unknown etiology. A wealth of evidence supports the concept that achalasia is an immune-mediated disease. According to this evidence, achalasia has been significantly associated with specific alleles of the human leukocyte antigen class II, PTPN22 and IL23R. Several studies have demonstrated association of the IL10 gene with different inflammatory disorders. Our aim was to evaluate the role of functional IL10 promoter polymorphisms in susceptibility to idiopathic achalasia. A case-control study was performed with the -1082, -819, and -592 IL10 promoter polymorphisms in 282 patients and 529 controls and in an independent replication set of 75 patients and 575 controls. The GCC haplotype of the IL10 promoter was reported to be associated with a lower risk of achalasia in the discovery sample (odds ratio [OR] = 0.79, 95% confidence interval [CI] = 0.64-0.98, p = 0.029). This association was validated in a replication set (OR = 0.69, 95% CI = 0.48-1.00, p = 0.04). In the combined analysis no heterogeneity was observed between the 2 sample sets and the GCC haplotype was significantly associated with the disease (OR(MH) = 0.76, 95% CI = 0.63-0.91, p = 0.003). Our results provide the first evidence for an association between IL10 promoter polymorphisms and idiopathic achalasia, suggesting that the interleukin-10 cytokine may contribute to the pathogenesis of this disease.
authors.affiliation: Clinical Immunology Department, Instituto de Investigación Sanitaria San Carlos, Madrid, Spain.
authors.forename: Concepción
authors.initials: C
authors.lastname: Nuñez
authors.forename: María Asunción
authors.initials: MA
authors.lastname: García-González
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Santiago
authors.forename: María Soledad
authors.initials: MS
authors.lastname: Benito
authors.forename: Fermín
authors.initials: F
authors.lastname: Mearín
authors.forename: Emilio G
authors.initials: EG
authors.lastname: de la Concha
authors.forename: Julio Pérez
authors.initials: JP
authors.lastname: de la Serna
authors.forename: Antonio Ruiz
authors.initials: AR
authors.lastname: de León
authors.forename: Elena
authors.initials: E
authors.lastname: Urcelay
authors.forename: Ana G
authors.initials: AG
authors.lastname: Vigo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D004931:Esophageal Achalasia / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007109:Immunity / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D013030:Spain
chemical_list: D016753:Interleukin-10