Publication: MTNR1B geni nükleotit polimorfizmlarinin nonalkolik yağlı karaciğer hastalığı etyopatogenezi ile ilişkisi
Abstract
Amaç: Geniş bir spektruma sahip olan Non-alkolik yağlı karaciğer hastalığı (NAFLD); basit yağlanma, steatoz, fibroz oluşumu ile bazı ileri vakalarda siroz ve hepatoselüler karsinomayı kapsayan bir hastalık grubudur. NAFLD gelişimi insülin direnci, tip 2 diyabet (T2D), obezite ve metabolik sendrom ile yakından ilişkilidir. Non-alkolik steatohepatit (NASH) NAFLD’ın ileri evre bir hastalığıdır. Melatonin reseptör 1B (MTNR1B) geninin T2D gelişiminde güçlü bir aday gen olduğu iyi bilinmektedir. Bu gene ait rs1387153 (C/ T), rs2166706 (C/ T) ve rs10830963 (C/ G) polimorfizmleri artmış açlık glikozu (hiperglisemi), azalmış insülin salınımı ve T2D riski ile ilişkilendirilmiştir. Bu çalışmayla NASH’li hastalarda NAFLD etyolojisinde etkili olan komponentlerle ilişkilendirilmiş MTNR1B geni polimorfizmlerinin NASH gelişimi ve klinik özellikleri ile olası ilişkisini araştırmayı amaçlamaktayız. Gereç ve Yöntem: Çalışmamıza yaş ve cinsiyet eşleştirilmiş 100 biyopsi kanıtlı NASH hastası ve 100 sağlıklı kontrol birey dahil edilmiştir. Litaratürde ilk kez MTNR1B rs1387153 (C/ T), rs2166706 (C/ T) ve rs10830963 (C/ G) polimorfizmlerine ait genotipleri tek bir reaksiyonda tespit eden mültipleks tek baz uzatma paneli (Multiplex - Single Base Primer Extension, SBE) dizayn edilmiştir. Bulgular: Hasta ve kontrol gruplarında MTNR1B polimorfizmlerine ait genotip ve allel frekansları arasında istatiksel olarak anlamlı bir fark saptanmamıştır. Ayrıca NASH’in histolojik, demografik ve klinik alt grupları arasında da herhangi bir ilişki gözlenmemiştir. Sonuçlar: MTNR1B’daki mevcut polimorfizmlerin NASH komponentleri ile ilişkili olmasına rağmen hastalığın patogenezinde rol oynamadığı gösterilmiştir. Ancak bu çalışma MTNR1B’nın NASH ile ilişkisinin sorgulandığı ilk araştırmadır. Bu nedenle bu bulguların ve gene ait diğer polimorfizmlerin farklı coğrafi ve etnik daha geniş gruplarda çalışılarak test edilmesi gerekmektedir.
Aim: Non-alcoholic fatty liver disease (NAFLD) has a broad range spectrum comprised of simple steatosis, steatohepatitis, fibrosis formation. In some severe cases of NAFLD may lead to cirrhosis and hepatocellular carcinoma. NAFLD development is closely associated with insulin resistance, type II diabetes (T2D), obesity and metabolic syndrome. Non-alcoholic steatohepatitis (NASH) is a severe form of NAFLD. Melatonin receptor 1B (MTNR1B) gene has known to be a strong candidate gene for T2D development. MTNR1B polymorphisms [rs1387153 (C/ T), rs2166706 (C/ T) and rs10830963 (C/ G)], were associated with decreased insulin release, elevated fasting glucose and increased risk of type 2 diabetes. We purposed to investigate potential relationship with MTNR1B polymorphisms to NASH development and clinical features in this study. Methods: 100 biopsy-proven NASH patients and 100 age and gender-matched controls were enrolled in our study. For the first time in the literature, multiplex single base primer extension (Multiplex SBE) panel was designed to detect MTNR1B polymorphisms in one reaction. Results: Genotype and allele frequencies of MTNR1B polymorphisms were not significantly different between case and controls. They were also not found to be associated with histological, demographic and clinical subgroups of NASH. Conclusion: Although MTNR1B polymorphisms are related to NASH components, they appears not to be involved in pathogenesis of NASH. But this study is the first investigation of examining the association of MTNR1B with NASH. Therefore, these findings and other MTNR1B polymorphisms should be tested in the larger study groups in the different geographic area and ethnic populations.
Aim: Non-alcoholic fatty liver disease (NAFLD) has a broad range spectrum comprised of simple steatosis, steatohepatitis, fibrosis formation. In some severe cases of NAFLD may lead to cirrhosis and hepatocellular carcinoma. NAFLD development is closely associated with insulin resistance, type II diabetes (T2D), obesity and metabolic syndrome. Non-alcoholic steatohepatitis (NASH) is a severe form of NAFLD. Melatonin receptor 1B (MTNR1B) gene has known to be a strong candidate gene for T2D development. MTNR1B polymorphisms [rs1387153 (C/ T), rs2166706 (C/ T) and rs10830963 (C/ G)], were associated with decreased insulin release, elevated fasting glucose and increased risk of type 2 diabetes. We purposed to investigate potential relationship with MTNR1B polymorphisms to NASH development and clinical features in this study. Methods: 100 biopsy-proven NASH patients and 100 age and gender-matched controls were enrolled in our study. For the first time in the literature, multiplex single base primer extension (Multiplex SBE) panel was designed to detect MTNR1B polymorphisms in one reaction. Results: Genotype and allele frequencies of MTNR1B polymorphisms were not significantly different between case and controls. They were also not found to be associated with histological, demographic and clinical subgroups of NASH. Conclusion: Although MTNR1B polymorphisms are related to NASH components, they appears not to be involved in pathogenesis of NASH. But this study is the first investigation of examining the association of MTNR1B with NASH. Therefore, these findings and other MTNR1B polymorphisms should be tested in the larger study groups in the different geographic area and ethnic populations.