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A functional polymorphism (rs6554199) located in the c-kit gene was associated with achalasia in a Turkish cohort. Our aim was to replicate this result in a large cohort of Spanish patients and controls. A case-control study was performed with 282 Spanish white unrelated patients and 687 healthy controls. All were genotyped for SNP rs6554199 using a TaqMan Assay. No association was found in our study (T allele frequency in patients and controls: 47.3% vs. 49.4%; OR=0.92, p=0.41). The finding that the T allele of the c-kit rs6554199 polymorphism could be associated with achalasia as reported in a Turkish population could not be replicated in a Spanish cohort. Although ethnic differences might explain these data, the sample size that compromised the statistical power in the Turkish cohort and is higher in our study, led us to suggest that the reported association seems to be a false positive., (Copyright © 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2011 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Background: Idiopathic achalasia is a primary esophageal motor disorder of unknown etiology. Different evidences have been reported in support of achalasia as the result of an autoimmune and inflammatory process leading to neuronal cell loss. According to this, idiopathic achalasia has been significantly associated with specific alleles of the human leukocyte antigen system class II, although few reports studying association with other loci can be found in the literature. Recent studies have shown association of a non-synonymous polymorphism within the IL23R gene with different chronic inflammatory disorders, including Barrett's esophagus. The purpose of this study was to assess whether the IL23R coding variant Arg381Gln polymorphism is involved in susceptibility to idiopathic achalasia., Methods: We performed a case-control study including 262 patients with idiopathic achalasia and 802 healthy subjects, all of them white Spaniards. Achalasia patients were diagnosed on the basis of clinical, radiographic, endoscopic, and manometric criteria. All samples were genotyped for the IL23R Arg381Gln polymorphism using TaqMan technology., Key Results: The minor allele of the Arg381Gln polymorphism was significantly increased in patients compared with healthy controls (OR = 1.46, 95% CI = 1.01-2.11, P = 0.036). This association seems to be specific to male patients with disease onset after 40 years (OR = 2.33, 95% CI = 1.29-4.16, P = 0.002)., Conclusions & Inferences: Our results suggest a role of IL23R in idiopathic achalasia predisposition and extend the evidence of the general influence of this gene in autoimmune and inflammatory diseases.