Publication: Glipikan 3 polimorfizminin Türk popülasyonundaki hepatoselüler karsinoma hastalarında genetik belirteç olarak önemi
Abstract
Amaç: Tez çalışmasındaki amacımız GPC3 rs2267531 promoter polimorfizmi ile ülkemizdeki HCC’nin primer sebebi olan kronik hepatit B virüsü (HBV) enfeksiyonu ve hepatoselüler kanser (HCC) ile olan olası ilişkisini araştırmaktır. Gereç ve Yöntem: Çalışmamıza 57 kronik hepatit B’li hasta, 84 HBV etiyolojili HCC (HBV- HCC), 35 HBV etiyolojili siroz (HBV-siroz) hastası ve 120 sağlıklı birey dahil edilmiştir. Genotipler rhAmp SNP allelik diskriminasyon yöntemi ile tayin edilmiş, elde edilen sonuçlar sanger sekans metoduyla doğrulanmıştır. Genotiplerin tüm gruplar arasındaki karşılaştırılmalarında lojistik regresyon analizi yapılarak yaş ve cinsiyet düzeltmesi yapılmıştır. Bulgular: Dominant genetik modele göre kronik hepatit B’li hastalar ile kontroller karşılaştırıldığında GPC3 rs2267531 C/ C genotipi anlamlı olarak kontrollerde yüksek saptanmıştır(aOR=0.484, CI=0.242-0.968, P=0.040). Benzer şekilde baskın genetik modele göre kontrol grubunda GPC3 rs2267531 C/ C genotip frekansı anlamlı olarak HBV etiyolojili siroz grubundakilere göre yüksek saptanmıştır(aOR=0.355, CI=0.130-0.965, P=0.042). Overdominant modelde G/ C genotip frekansı anlamlı olarak kontrollerde HBV etiyolojili HCC grubuna göre yüksek saptanmıştır(aOR=5.970, CI=1.272-28.016, P=0.024). Sonuç: Bu çalışmayla literatürde ilk kez Türk popülasyonunda GPC3 rs2267531 promoter polimorfizmine ait varyantlar analiz edilmiştir. Sonuçlarımıza göre, GPC3 rs2267531 promoter polimorfizmi HCC için bir risk oluşturmamaktadır. Aynı zamanda HBV- siroz, kronik hepatit B’li ve HCC’li hasta grupları arasında da polimorfizm açısında anlamlı bir fark saptanmamıştır. Bununla birlikte GPC3 rs2267531 promoter polimorfizmi C/ C genotipi kronik hepatit B ve HBV-siroz gelişimine karşı, G/ C genotipi ise HBV-HCC gelişimine karşı koruyucu olarak saptanmıştır. Bulgularımızın farklı coğrafi ve etnik gruplarda yapılacak çalışmalarla doğrulanması gerekmektedir.
Aim: Our aim in this thesis is to investigate the possible relationship between GPC3 rs2267531 promoter polymorphism and chronic HBV infection and HCC, which is the primary cause of HCC in our country. Materials and Methods: Our study included 57 patients with chronic hepatitis B, 84 patients with HBV-HCC, 35 patients with HBV-cirrhosis and 120 healthy individuals. Genotypes were determined by the rhAmp SNP allelic discrimination method, and the results were confirmed by the sanger sequencing method. Logistic regression analysis was performed for the comparison of genotypes between all groups, and age and gender corrections were made. Findings: According to the dominant genetic model, when patients with Chronic Hepatitis B and controls were compared, the GPC3 rs2267531 C/ C genotype was found to be significantly higher in controls(aOR=0.484, CI=0.242-0.968, P=0.040). Similarly, according to the dominant genetic model, the frequency of the GPC3 rs2267531 C/ C genotype was significantly higher in the control group than in the HBV-cirrhosis group(aOR=0.355, CI=0.130-0.965, P=0.042). In the overdominant model, the G/ C genotype frequency was significantly higher in controls than in the HBV-HCC group(aOR=5.970, CI=1.272-28.016, P=0.024). Result: The GPC3 rs2267531 promoter polymorphism doesn’t pose a risk for HCC. No significant difference was found in terms of polymorphism between the patient groups with with HBV-cirrhosis, chronic hepatitis B and HCC. Finally, GPC3 rs2267531 promoter polymorphism was found to be protective against the C/ C genotype against the development of chronic hepatitis B and HBV-cirrhosis and G/ C genotype was found to be protective against the development of HBV-HCC.
Aim: Our aim in this thesis is to investigate the possible relationship between GPC3 rs2267531 promoter polymorphism and chronic HBV infection and HCC, which is the primary cause of HCC in our country. Materials and Methods: Our study included 57 patients with chronic hepatitis B, 84 patients with HBV-HCC, 35 patients with HBV-cirrhosis and 120 healthy individuals. Genotypes were determined by the rhAmp SNP allelic discrimination method, and the results were confirmed by the sanger sequencing method. Logistic regression analysis was performed for the comparison of genotypes between all groups, and age and gender corrections were made. Findings: According to the dominant genetic model, when patients with Chronic Hepatitis B and controls were compared, the GPC3 rs2267531 C/ C genotype was found to be significantly higher in controls(aOR=0.484, CI=0.242-0.968, P=0.040). Similarly, according to the dominant genetic model, the frequency of the GPC3 rs2267531 C/ C genotype was significantly higher in the control group than in the HBV-cirrhosis group(aOR=0.355, CI=0.130-0.965, P=0.042). In the overdominant model, the G/ C genotype frequency was significantly higher in controls than in the HBV-HCC group(aOR=5.970, CI=1.272-28.016, P=0.024). Result: The GPC3 rs2267531 promoter polymorphism doesn’t pose a risk for HCC. No significant difference was found in terms of polymorphism between the patient groups with with HBV-cirrhosis, chronic hepatitis B and HCC. Finally, GPC3 rs2267531 promoter polymorphism was found to be protective against the C/ C genotype against the development of chronic hepatitis B and HBV-cirrhosis and G/ C genotype was found to be protective against the development of HBV-HCC.