Association of Pregnane X Receptor (Pxr) with Esophageal Disease in An Irish Population
Mahwash Babar*1,2, John V. Reynolds1, Ross Mcmanus2
1Surgery, St. James's Hospital, Dublin, Dublin, Ireland; 2Clinical Medicine, Trinity College, Dublin, Ireland
It has been shown that acid and bile reflux play a role in oesophageal inflammation and carcinogenesis and enhanced expression of bile acid/xenobiotic receptors (Farnesoid X receptor, FXR and Retinoid X receptor, RXR) has been shown in Barrett’s esophagus. These receptors act as transcriptional regulators of Cytochrome P450 3A4 (CYP3A4) which is an important xenobiotic/drug metabolizing enzyme (DME). Genome Wide Association studies have shown genetic polymorphisms in DME to be linked with susceptibility to oesophageal carcinoma in the Chinese population. Here we examined the associaton of variants in the Pregnane X Receptor (PXR) gene, a member of the xenobiotic receptor family, and oesophageal disease in the Irish population. We genotyped the SNP -25385 (C/T) (rs3814055) which is a promoter polymorphism in the PXR gene in 1614 individuals (EAC, n=186, Barrett’s,n=186, Reflux oesophagitis, n=180, Controls,n=876). The data from all loci conformed to Hardy-Weinberg Equilibrium in all the populations. When the allele frequencies between the patients and the healthy controls were compared, the reflux population showed an increased frequency of the C allele which reached significance when compared to the random irish control population (59 vs 65, p=0.008, OR=1.53). No significant association was observed between the other groups and the control population for this locus. These preliminary data show a suggestive association of the PXR gene polymorphism with reflux in the Irish population.