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

Yıl 2019, Cilt: 50 Sayı: 1, 7 - 12, 14.03.2019

Fatma Selcen Önder , Baha Oral

https://doi.org/10.16948/zktipb.421432

Öz

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.

Anahtar Kelimeler

DNA Methylation, VEGF, FLT1, Gestational Diabetes, PLACENTA

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

Öz

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

Kaynakça

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