Notably, ECM1 strongly activates nuclear factor-��B signaling, a key immune regulator. Expression selleck catalog is upregulated in colorectal cancer and metastases, which implicates ECM1 in epithelial-stromal interaction[18]. Of note, the WTCCC observed modest association between these ECM1 SNPs and ankylosing spondylitis, a related inflammatory disorder (P = 0.0041 and 0.0044), respectively[13]. More recently, an association between the rs3737240 and rs13294 variants of ECM1 and UC susceptibility was reported in a GWAS by Fisher et al[15], with an OR of 1.3-1.4 for the homozygous carriage of the variant allele. rs3737240 and rs13294 encode substitutions T130M and G290S: Thr130, residing within a collagen IV binding domain, is conserved in primates, whereas Gly290 is not.
Finally, data about the pharmacogenetics of IBD are still limited. Resistance to steroids is associated with high expression of ��-glucocorticoid receptors (hGR��) and overexpression of MDR1 has been found in patients who fail steroid therapy and require surgery[19]. In contrast, according to our group��s earlier results, the presence of the DLG5 Arg30Gln variant allele, but not variants in ABCG2 or MDR1 genes, predicted resistance to steroids[20,21]. Vermeire et al[22] have reported a lack of association between the presence of NOD2 mutations and response to infliximab therapy, and later, the same group reported an association between the presence of Fas ligand -843C/T variant and response to infliximab[23].
In light of the lack of data in Eastern European countries, our aim was to investigate the prevalence of IRGM rs13361189, NKX2-3 rs10883365 and ECM1 rs13294 variants in large independent cohorts of Czech and Hungarian IBD patients. We also aimed to investigate a possible association between genotype and clinical phenotype, need for surgery, and response to medical therapy. MATERIALS AND METHODS Study population One thousand seven hundred and seven unrelated IBD patients (CD: n = 810, age: 37.1 �� 12.6 years, duration: 10.7 �� 8.4 years and UC: n = 428, age: 43.7 �� 15.0 years, duration: 12.6 �� 9.9 years) and 469 healthy subjects (blood donors) from Hungary and the Czech Republic were investigated. The clinical data of the CD and UC patients are presented in Table Table1.1. Cilengitide A detailed clinical phenotype was available in 789 CD and 422 UC patients. Table 1 Clinical characteristics of patients with inflammatory bowel diseases The diagnosis was based on the Lennard-Jones criteria[24].