From one cohort there was less DNA available so that these SNPs could not be genotyped in that cohort and rs11110395 failed in some cases for technical reasons. Genotyping was performed using TaqMan assays on a TaqMan 7900 HT (Applied Biosystems, Foster City, California, USA). All reported p values are uncorrected unless stated otherwise. Statistical selleck chem inhibitor analysis Statistical significance in mRNA expression study was determined by the Student’s t-test or the non-parametric Mann-Whitney U test as appropriate. Correlation and regression analyses were used to determine the relationships between expression values. Statistical significance for correlation was determined by Spearman’s coefficient test. All statistical calculations were performed with GraphPad PRISM software (Graphpad Software, La Jolla, CA, USA).
Two-sided p-values <0.05 are considered statistically significant. Statistical analysis of the genetic association study was performed using 2-tailed ��2 tests of case vs. control allele and haplotype counts for tagging and functional SNPs in Haploview v4.0. [26]. P-values, odds ratios (OR) and 95% confidence intervals (95% CI) are shown. The Bonferroni method was used to correct for multiple testing. All tables show the uncorrected p-values. Results mRNA expression of FXR and its target gene SHP FXR and its target gene SHP were expressed both in the ileum and ascending colon of IBD patients in remission and controls. Expression levels of FXR and SHP were markedly lower in the right colon compared to the ileum (53% and 55% lower in the right colon, respectively).
There was no significant difference in ileal FXR expression between controls, CD and UC patients (Figure 1A). However, ileal expression of SHP was 50% lower in CD patients compared to controls (p=0.039), and 33% lower in UC patients compared to controls (p=0.21) (Figure 1B). A similar trend, although not significant, was observed in the colon (data not shown). FXR and its target genes are exclusively expressed in the differentiated enterocyte in the villi [15], [17], [19]. We, therefore, also correlated FXR and SHP mRNA expression to Villin expression, a marker exclusively expressed in differentiated enterocytes. Villin expression was associated with sucrose isomaltase (SI, another gene expressed in differentiated enterocytes) expression in controls, UC and CD patients (Figure 2A�CC).
Villin expression correlated Entinostat also with FXR expression in healthy controls. However, the correlation was lost in UC and CD patients (Figure 2D�CF). In addition, Villin expression showed significant correlation with SHP expression in healthy controls and UC patients, whereas the correlation was lost in CD patients (Figure 2G�CI). Similar results were found for the correlation between SI expression and either FXR or SHP (data not shown).