Gestasyonel Diyabette Genetik ve Epigenetik Değişimler

Gestasyonel Diyabet (GDM) ilk defa gebelikte teşhis edilen veya başlayan farklı derecelerdeki glukoz intöleransıdır. GDM tanısı alan gebelerde ve yeni doğanda komplikasyon oranı artar. GDM için birçok risk faktörü tespit edilmiş olup bunlar ileri anne yaşı, yüksek parite, önceki gebelikte GDM öyküsü, ya da makrozomik bebeğin erken doğumu, kısa boy, obezite, çoklu gebelik, gebelik sırasında yüksek kan basıncı ve ailede diyabet öyküsüdür. GDM prevelansı farklı populasyonlar arasında değişkenlik göstermekte olup bu değer % 7 ile % 17 arasında değişir. GDM sıklığının populasyonlar arasında değişkenlik göstermesinde, genetik ve epigenetik farklılıkların önemli rolü olduğu düşünülmektedir. GDM ile ilgili yapılan genetik çalışmaların çoğu biyolojik olarak makul olan aday gen analizlerine dayanmaktadır. Bu çalışmaların birçoğunu içeren iki farklı meta-analiz gerçekleştirilmiş olup bu iki meta-analiz sonucunda GDM ile ilişki gösteren 8 gen tespit edilmiştir. Bu genler; TCF7L2, GCK, KCNJ11, KCNQ1, CDKAL1, IGF2BP2, MTNR1B ve IRS1’dir. Bu lokusların/genlerin tümü aynı zamanda Tip 2 Diyabet (T2DM) riski ile de ilişkilidir. GCK, KCNJ11, KCNQ1, MTNR1B, IGF2BP2, CDKAL1 ve TCF7L2’nin de dahil olduğu bu genlerin çoğunluğu, beta hücre fonksiyonu veya gelişimi için önemli olan proteinleri kodlamaktadır. Bunun yanı sıra epigenetik faktörlerin de GDM patogenezinde oldukça önemli rol oynadığını gösteren kanıtlar mevcuttur. Bu makalede GDM patogenezinde rolü olduğu düşünülen genetik ve epigenetik faktörler sunulmuştur.

Anahtar Kelimeler:

Gestasyonel diyabet, Genetik, Epigenetik

Genetic and Epigenetic Alterations in Gestational Diabetes

Gestational Diabetes is glucose intolerance that are diagnosed or started for the first time in pregnancy. In pregnancies diagnosed withgestational diabetes mellitus, complication rates increase in mother and newborn. Many risk factors have been identified for GDM.These include anemia, advanced maternal age, high parity, GDM in previous gestation, or premature birth of macrosomic baby, shortstature, obesity, multiple gestation, high blood pressure during pregnancy and family history of diabetes. The prevalence of GDM variesbetween different populations, with prevalence ranging from 7% to 17% in different populations. There is important role of genetic andepigenetic differences in variability of GDM prevalence between populations.Most of the genetic studies on GDM focus on biologically plausible candidate gene analyzes. Two different meta-analyzes involving amajority of these studies were performed, and these meta-analyzes revealed 8 genes associated with GDM. These genes are; TCF7L2,GCK, KCNJ11, KCNQ1, CDKAL1, IGF2BP2, MTNR1B and IRS1. All of these locations are also related to the T2DM risk. The majorityof these genes, including GCK, KCNJ11, KCNQ1, MTNR1B, IGF2BP2, CDKAL1 and TCF7L2, encode proteins that are important forbeta cell function or development. There is also evidence that epigenetic factors play an important role in the pathogenesis of GDM. Inthis article, genetic and epigenetic factors thought to play a role in the pathogenesis of GDM are presented.

Keywords:

Gestational diabetes, Genetics, Epigenetics,

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