Investigation of the relationship between chronic hepatitis B virus infection with HLA gene rs3077 and rs9277535 polymorphisms.

TEZ10822Tez (Doktora) -- Çukurova Üniversitesi, Adana, 2016.Kaynakça (s. 85-104) var.x, 105 s. : res. (bzs. rnk.), tablo ; 29 cm.Hepatit B Virüs (HBV) enfeksiyonu dünya genelinde yaklaşık 350 milyon insanı etkilemektedir. Kronik hepatit B (KHB) taşıyıcılarının %10-15’inde karaciğer sirozu, karaciğer bozukluğu ve hepatoselüler kanser gelişebilmektedir. HLA genindeki varyantlar HLA mRNA ekspresyonunu ve antijen sunumunu etkilemektedir. Bu vaka-kontrol çalışmasında HLA rs3077 ve rs9277535 polimorfizmlerininin HBV enfeksiyonunun kronikleşmesindeki etkisi araştırılmıştır. 294 KHB’li hasta grubu ile 234 doğal bağışık kontrol grubu RT-PCR (Gerçek zamanlı polimeraz zincir reaksiyon) yöntemi ile çalışılmıştır. HBV grubu ile kontrol grubu arasında rs9277535 alel sıklığı yönünden anlamlı bir fark bulunmuştur (P=0.05). Ayrıca AG haplotip bloğunun HBV’nin kronikleşmesine karşı koruyucu etkiye sahip olduğu tespit edilmiştir (P=0.003). Bu çalışma kontrol grubunun doğal bağışık bireylerden oluştuğu beyaz popülasyondaki ilk çalışmadır. Bu çalışmada HLA-DPB1 geni rs9277535 A alelinin özellikle erkeklerde majör bir risk faktörü olduğu belirlenmiştir. Fakat rs3077 polimorfizminin anlamlı bir etkisi belirlenememiştir.Hepatitis B virus (HBV) affects approximately 350 million people worldwide. 10–15% of chronic carriers develop liver cirrhosis (LC), liver failure and hepatocellular carcinoma (HCC). Genetic variants in HLA genes influence HLA mRNA expression which might also affect antigen presentation. We evaluated the association between HLA gene polymorphisms and the risk for persistent HBV infection. HLA gene polymorphisms were investigated in a case–control study of 294 chronic HBV carriers and 234 persons with HBV natural clearance by using a real-time polymerase chain reaction (RT-PCR). There was a significant association between the control and the case groups for rs9277535 allele frequencies (P=0.05), but not significant for rs3077. Additionally, the AG haplotype block showed a protective effect against the risk of persistent HBV infection (P=0.003). Our results demonstrate for the first time that HLA-DPB1 gene rs9277535 A allele, especially in male, has a major effect on the risk of persistent HBV infection, but not for rs3077.Bu çalışma Ç.Ü. Bilimsel Araştırma Projeleri Birimi tarafından desteklenmiştir. Proje No: FEF2013D16

The association between the survivin-31G/C promoter polymorphism and hepatocellular carcinoma risk in a Turkish population

WOS: 000298169300022PubMed ID: 21296634Background: Survivin, a member of the inhibitor of apoptosis protein family, functions as a key regulator of apoptosis and cell cycle regulation. A common single nucleotide polymorphism (-31G>C) at the survivin promoter has been extensively studied in various cancers and reported to influence survivin expression, but its association with hepatocellular carinoma (HCC) has yet to be investigated. The aim of the present study was to investigate whether this polymorphism could be involved in the risk of HCC susceptibilty. Methods: The genotype frequency of survivin -31G>C polymorphism was determined by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 160 subjects with HCC and 241 cancer-free control subjects matched on age, gender, smoking and alcohol status. Results: No statistically significant differences were found in the genotype distributions of the survivin -31G>C polymorphism among HCC and cancer-free control subjects (p = 0.28). Conclusion: Our results demonstrate for the first time that the survivin -31G/C polymorphism have not been any major role in genetic susceptibilty to hepatocellular carcinogenesis, at least in the population studied here. (C) 2011 Elsevier Ltd. All rights reserved.Cukurova UniversityCukurova University [FEF2008D4]The authors thank all the subjects who participated in this study. This work was supported by Cukurova University Research Fund FEF2008D4

CYP2C19 fonksiyonel polimorfizminin Helicobacter pylori eradikasyonu üzerine etkisi

Proton pompa inhibitörler, büyük ölçüde karaciğerde bulunan sitokrom P450 2C19 (CYP2C19) enzimi tarafından metabolize edilirler. Sitokrom P450 2C19 enziminin fonksiyonel polimorfizmi proton pompa inhibitörleri asit'baskılayıcı etkilerini değiştirebilir. Bu çalışmada, sitokrom P450 2C19 polimorfizminin proton pompa inhibitörler'temelli tedavilerde Helikobakter pilori eradikasyonu üzerinde etkisini araştırmayı amaçladık. Yöntem: Bu çalışmada, Helikobakter pilori'ye bağlı kronik gastrit tanısı olan 105 hastada sitokrom P450 2C19 genotipinin sıklığını ve bu genotipin Helikobakter pilori eradikasyon oranını belirledik. Üst gastrointestinal endoskopi ve gastrik biyopsi her hastada uygulandı. Helikobakter pilori tanısı histolojik olarak konuldu. Hastalara lansoprazol, amoksisilin ve klaritromisin günde 2 kez olmak üzere 14 gün süreyle uygulandı. Helikobakter pilori eradikasyonunu belirlemek üzere tedaviden bir ay sonra tüm hastalara 13C üre-solunum testi yapıldı. sitokrom P450 2C19 polimorfizmi polimeraz zincir reaksiyonu temelli-RFLP yöntemi ile saptandı. Bulgular: Sitokrom P450 2C19 polimorfizmleri 3 gruba ayrıldı; hızlı metabolize edici, orta derecede metabolize edici ve yavaş metabolize edici olmak üzere. Hastalarımız arasında, hızlı metabolize edici %72 oranında, orta derecede metabolize edici %23 oranında ve yavaş metabolize edici ise %5 oranında belirlendi. Helikobakter pilori eradikasyon oranı hızlı metabolize edici grupta %70 oranında, orta derecede metabolize edici grupta %92 ve yavaş metabolize edici grupta ise %80 oranında saptandı. Sonuç: Bulgularımız hızlı metabolize edici grupta Helikobakter pilori eradikasyon oranının düşük olduğunu doğrulamaktadır. Tedavi öncesi sitokrom P450 2C19 genotipinin belirlenmesi tedavi başarısının öngörülmesi açısından yararlı olur. Hızlı metabolize edici hastalarda Helikobakter pilori eradikasyon oranını yükseltmek amacıyla alternatif tedaviler denenebilir.Proton pump inhibitors are mainly metabolized by cytochrome P450 2C19 in the liver. Recently, some studies have shown that the acid�suppressing effect of proton pump inhibitors are influenced by a functional polymorphism of cytochrome P450 2C19. The aim of the present study was to investigate the effect of cytochrome P450 2C19 polymorphism on Helicobacter pylori eradication in patients who received proton pump inhibitors�based triple therapy. Methods: We determined the incidence of cytochrome P450 2C19 genotypes and the effect of cytochrome P450 2C19 genotypes on Helicobacter pylori eradication rates in 105 patients with Helicobacter pylori-positive chronic gastritis. Upper endoscopic procedure and gastric biopsies were performed in all patients. Helicobacter pylori was demonstrated histologically. Lansoprazole, amoxicillin and clarithromycin twice a day for 14 days were prescribed for those found to be infected with Helicobacter pylori. More than one month after the medication, a 13C urea breath test was conducted to examine the success or failure of the eradication treatment. Cytochrome P450 2C19 polymorphism was analyzed by the polymerase chain reaction�restriction fragment length polymorphism method. Results: The genotypes of cytochrome P450 2C19 were classified into the three groups, as rapid extensive metabolizer, intermediate metabolizer and poor metabolizer. In our patient population, the frequencies of rapid extensive metabolizer, intermediate metabolizer and poor metabolizer were 72%, 23% and 5%, respectively. The eradication rate was 70.0% for rapid extensive metabolizer, 92% for intermediate metabolizer and 80% for poor metabolizer. The eradication rate was highest in intermediate metabolizer patients. Conclusions: The present study confirmed the low eradication rate for rapid extensive metabolizer. Our findings provide evidence that the cytochrome P450 2C19 genotype is useful to predict the success of treatment. For the rapid extensive metabolizer group, alternative regimens can be tried to increase the Helicobacter pylori eradication rates

The role of Interleukin 28B gene polymorphism in Turkish patients with hepatocellular carcinoma

Background and aim. Multiple risk factors lead to hepatocellular carcinoma (HCC) including viral infections, mutation and single nucleotide polymorphisms (SNPs). Interleukin 28B (IL28B) gene rs12979860 polymorphism has been shown to be associated with HCC in the different populations, but its association with HCC has not been investigated in the Turkish population. We investigated whether the rs12979860 polymorphism of IL28B gene affects the risk of HCC.Material and method. We performed genotyping analysis using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in a hospital-based case-control study of 187 confirmed HCC patients and 208 healthy subjects (cancer and viral infection negative) in the Turkish population.Results. The allele and genotype analysis showed no significant differences between the risk of HCC and IL28B gene rs12979860 polymorphism (OR = 1.10; 95% 0.59-2.08 P = 0.76 for genotype). However, in the HBV-related HCC subgroup, the TT genotype increased a 1.46-fold the risk of developing HCC, but not statistically significant (OR = 1.46; 95% 0.71-2.97 P = 0.30). Furthermore, no significant differences were found between clinical findings, and sex in comparison with the IL28B genotypes in HCC group (P > 0.05).Conclusion. Our results suggest, for the first time, that no significant association were found between IL28B rs12979860 genotypes with the risk of developing HCC in Turkish patients. Further independent investigations are required to clarify the possible role of IL28B gene rs12979860 polymorphism on the risk of developing HCC in a larger series and also in patients of different ethnic origins