Genetic polymorphisms of cytochrome P4501-3 (CYP1-3) and phase II enzymes in turkish ulcerative colitis patients


Tezin Türü: Yüksek Lisans

Tezin Yürütüldüğü Kurum: Pamukkale Üniversitesi, Fen-Edebiyat Fakültesi, Biyoloji Bölümü, Türkiye

Tezin Onay Tarihi: 2010

Tezin Dili: Türkçe

Öğrenci: Özgen Büyükgöze

Danışman: Alaattin Şen

Özet:

Genetic polymorphisms of drug metabolizing enzymes, such as CYPs, play major roles in the variations of drug responsiveness in human. The aim of the present study was to determine the prevalence of the most common allelic variants of the polymorphic CYP enzymes 1A1*2A, 2C9*3, 2D6*2, mEPH*3, mEPH*4, 3A4*1B, GSTT1, GSTM1, TPMT*2, TPMT*3B, TPMT*3C, XRCC1 codon 194, XRCC1 codon 399 and to predict the allel frequency for each polymorphism in the Turkish population. For this purpose, whole blood samples were collected from 200 healthy volunteers and 115 case for CYP1A1*2A, 130 healthy volunteers and 115 case with ulcerative colitis for 2D6*2, 2C9*3, mEPH*3, mEPH*4, 3A4*1B, GSTT1, GSTM1, TPMT*2, TPMT*3B, TPMT*3C, XRCC1 codon 194, XRCC1 codon 399 representing Turkish population and genomic DNA for each subject was isolated and was used to determine the frequency and odds ratio of these genes allelic variants by the PCR-RFLP. The odds ratio for 2D6*2, 2C9*3, mEPH*4, 3A4*1B, GSTM1, TPMT*2, TPMT*3B, TPMT*3C, XRCC1 codon 194 were determined as 1.56; 1.76; 1.14; 0; 1.44; 0; 0; 0; 1.71. These results suggested that these genotypes are not possible factor for risk of incidence of ulcerative colitis. On the other hand, the odds ratio?s, for 1A1*2A, mEPH*3, GSTT1 and XRCC codon 399 were found to be as 3.5; 3.0881; 2.0491. These results suggested that the genotypes of these genes might be a possible factor for the risk of incidence of ulcerative colitis since we found that these variant genotypes had a 6.42; 4.62; 1.87 and 2.28 fold higher risks of developing ulcerative colitis than these with the wild type genotype .