Sitokrom P450 2c19 (Cyp2c19) Genetik Polimorfizmlerinin Ülseratif Kolit ve Crohn Hastalığındaki Etkileri

Abstract

Inflammatory bowel diseases (IBD) are diseases characterized by chronic inflammation of the intestinal mucosa. Ulcerative colitis (UC) and Crohn's disease (CH) are clinical entities presenting different characteristics. Genetic factors play an important role in the pathogenesis of inflammatory conditions. Detection of genetic polymorphisms associated with these disorders may help understand the pathophysiology, as well as may guide the diagnosis and individualized treatment. CYP2C19 is an enzyme that is partially responsible for the synthesis of epoxyieicosatrienoic acids (EETs) with vasodilatory and anti-inflammatory properties. Various studies have shown that acute or chronic inflammation can modulate activities of CYP enzymes. CYP2C19 genetic variants have been reported among risk factors for inflammatory diseases, such as Behçet’s disease, diabetik retinopathy, coronary artery disese and preeclampsia. The aim of this study is to examine the effects of genetic polymorphisms of CYP 2C19 (CYP2C19*2 and *17) in patients with UC and CH. Healthy volunteers (n=110) as the control group and patients with IBD (n=131) were included. PCR and restriction fragment length polymorpihsm analysis were used for genetic analysis. There were no significant differences among the control, UC and CD groups in terms of distribution of CYP2C19*2 or *17 alleles or genotypes. In CH group, while ileum involvement was about 20% and colon/ileocolon involvement was around 80% in patients with the wild-type genotype, the respective ratios in non-wild-type patients were about 60% and 40% (p<0,05). There was a statistically significant distribution difference for a higher frequency ( 25% vs. 10 %) of surgical resection in patients with the wild-type (*1/*1) genotype, as compared to the patients with other genotypes (p=0,02). There were no significant differences among genotype groups for other clinical features, such as the age at the diagnosis, the type of medical treatment applied, or presence of extra-intestinal findings. Our results may suggest that CYP2C19*2 and *17 polymorphisms may be useful biomarkers in the diagnosis, treatment and follow-up of patients with IBD.