Fatma selcen ÖNDER, Baha ORAL

Plasental Anjiogenezde Rol Alan Genlerin Gestasyonel Diyabeti Olan Gebelerde DNA Metilasyon Profilleri

AMAÇ: Gestasyonel diyabet için erken tanı ve tedavi modalitelerinin geliştirilememesinin nedeni etiyopatolojilerinin aydınlatılamamış olmasıdır. Bu patolojilerde plasentanın rolünü tanımlamak önemlidir. Plasenta genetik ve epigenetik faktörlerin etkisinde fetal gelişimi belirler.DNA metilasyonu değiştirilebilir epigenetik mekanizmalardandır. Günümüzde tanı ve tedavi amaçlı kullanılmaktadır. Çalışmamızda GDM (Gestasyonel Diyabet) gebelerde, plasental anjiogenezde etkili genlerden VEGF(Vaskuler Endotelyal Büyüme Faktörü), PIGF(Plasental Büyüme Faktörü) ve sFLT-1(soluble fms like tirozinkinaz)’nin DNA metilasyon değişiklikleri değerlendirilecektir.MATERYAL VE METOD: 2016-2017 tarihlerinde Süleyman Demirel Üniversitesi Kadın Hastalıkları ve Doğum Bölümü’nden takipli; 15 GDM tanılı ve 17 sağlıklı gebeden plasental örnekler alınmıştır. DNA metilasyon düzeyleri ‘Yeni Nesil Sekanslama’ ile belirlenmiştir. Verilerin dağılımlarına göre Manny Whitney U analizi; veriler arasındaki ilişkiler için Spearman korelasyon analizi kullanılmıştır.BULGULAR: Genlerin metilasyon oranları ile yaş, gebelik haftası, bebeğin cinsiyet ve ağırlığı arasında ikililer arasında anlamlı ilişki saptanmamıştır(p>0.05). Plasenta ağırlığı artarken sFLT-1 geninin P92186.Pozisyondaki promoter metilasyon düzeyinin azaldığı görülmüştür. PIGF geninin metilasyon değerlerinde gruplar arasında anlamlı fark bulunmamaktadır. sFLT 1 geninin bölgesel analizlerine göre P92186. , P92344. , P92456. pozisyonlarındaki primer noktalarının hipometile; VEGF geninin bölgesel analizlerine göre P92668. , P92710. , P92863. pozisyonlarındaki primer noktalarının hipermetile olduğu saptanmıştır. SONUÇ: Bulgularımız literatürle uyumludur ve anjiogenezde etkili genlerin bazı lokuslarındaki DNA metilasyon değişimlerinin GDM patogenezindeki yerine katkı sağlamıştır. Ancak prediktif değere ulaşılabilmesi için, geniş hasta gruplarıyla yapılacak genom çalışmaları ile ilgili gen bölgeleri netleştirilmelidir.

Anahtar Kelimeler:

DNA METILASYONU, Gestasyonel Diyabet, VEGF, s-FLT1, PLASENTA

DNA METHYLATION PROFILES OF GENES EFFECTIVE IN PLACENTAL ANGIOGENESIS FOR PREGNANTS WITH GESTATIONAL DIABETES

The reason of absence preventive processes from GDM and early treatment modalities is unsettled ethiopathologies. Defining the role of the placenta is important for these pathologies. Fetal growth is adjusted due to placental genetic and epigenetic factors.PURPOSE: DNA methylation which is an epigenetic mechanism, is modifiable and utiziable for diagnosis and treatment recently. DNA methylation changes of VEGF, sFLT-1, PIGF genes, have roles on placentation were evaluated according to GDM MATERIAL and METHOD: All placental samples had taken from pregnants who routinely followed at Suleyman Demirel University Gynecology and Obstetrics Department, compatible with study criteria and diagnosed as GDM (n=15) and healthy pregnants (n=17). DNA Methylation levels were analysed by ‘New Generation DNA Sequencing’ method. Data collections analysed via SPSS 23 programme. Because of data distrubution Manny Whitney U tests are used for means; SPEARMAN correlation analysis is used to reveal relation between datas.RESULT: The methylation levels were not changed significantly due to demographic characteristics. The analyses that examine differences in methylation levels of PIGF were established no statistically significant difference. There was statistically significant difference in levels of methylation of sFLT-1 gene at the position of P92186. , P92344. , P92456. primer regions as hypomethylated and VEGF gene at the position of P92668. , P92710. , P92863. primer regions as hypermethylated. CONCLUSION: The findings of our study indicates changes of DNA methylation in some regions of VEGF, sFLT-1 genes and it is compatible with literature. But clarifying of related regions of genes via whole genom studies with a large population is necessary to reach predictive values.

Keywords:

DNA Methylation, VEGF, FLT1, Gestational Diabetes, PLACENTA,

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