rs2302009

rs2302009 is a SNP located in the 3' untranslated region of the CCL26 gene. This gene (and this SNP) were discovered to be strongly associated with 117 patients with eosinophilic esophagitis, a form of esophagitis (or inflammation of the esophagus) that shares many symptoms with gastroesophageal reflux disease (GERD). rs2302009(G) is the risk allele. The rs2302009(G;G) homozygous genotype is the most predisposed to developing eosinophilic esophagitis (odds ratio 4.55, CI 1.71–12.39). The heterozgyote (rs2302009(G;T)) genotype's risk was indistinguishable statistically from the normal rs23020099(T;T) genotype.

C;C

4.6x risk of an inflammation of the esophagus that shares many symptoms with gastroesophageal reflux disease

A;C

Eosinophilic esophagitis (EE) is an emerging worldwide disease, as documented by recent case series from Switzerland, Australia, Canada, Japan, England, and the US (1–4). Of concern, EE appears to be a growing health problem with an annual incidence of at least 1 in 10,000 children (5). The primary symptoms of EE (chest and abdominal pain, dysphagia, heartburn, vomiting, and food impaction) are also observed in patients with chronic esophagitis (CE) including gastroesophageal reflux disease (GERD) (6–8). However, in contrast to GERD, EE occurs more frequently in males (80%), appears to have a common familial form, has a high rate of associated atopic disease (70%), and is typically associated with a normal pH probe recording of the esophagus (5, 9, 10) In the 3? untranslated region, one SNP (rs2302009, 2,496 T?G) was present in 20% of the white population. Therefore, we genotyped this SNP in patients with EE and control individuals without EE (Table 1). Genotypes of the SNP 2,496 T?G were in Hardy-Weinberg equilibrium in both EE patients and unrelated controls. Notably, the allele G was overrepresented in patients with EE compared with race/ethnicity–matched controls (32.1% versus 22.4%, P = 0.0069). Additionally, the frequency for genotype GG was significantly higher in patients with EE (odds ratio 4.55, 95% confidence interval 1.71–12.39, P = 0.001). The GG genotype was not predominant in atopic EE patients; of the 16 GG individuals identified, there were 7 and 9 allergen-sensitized and nonsensitized individuals, respectively. This suggests that the association of this SNP with EE is not dependent on atopic status. In order to validate the case-control results that could generate false positives due to population stratification, a family-based transmission disequilibrium test was conducted (27). From heterozygous parents, the allele G was preferentially transmitted to affected individuals compared with the alternative allele T (39 versus 18, P = 0.0054). The odds ratio was 2.13 (95% confidence interval 1.57–2.69). Taken together, the results obtained from both case-control and family-based association analyses suggest that the eotaxin-3 gene may be associated with susceptibility to EE. At present, of the 19 EE patients who were analyzed for eotaxin-3 production (Supplemental Table 1), 9 patients had a TG genotype and none had a GG genotype. Because only the GG genotype was associated with EE in the case-control analysis (Table 1), we would not expect a phenotypic difference between TG and TT; indeed, no phenotypic difference was observed Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1359059/