HNF1A Geni rs1169288 (A>C) Mutasyonunun MODY3 Üzerine Etkisinin Araştırılması

Year 2018, Issue: 1, 21 - 32, 30.09.2018

DENİZ Kanca Demirci , Hülya Yılmaz Aydoğan , Nurdan Gül , Yıldız Tütüncü Oğuz Öztürk , İlhan Satman

Abstract

Otozomal dominant kalıtımlı ve monogenik
bir diyabet formu olan Gençlerin Erişkin Başlangıçlı Diyabetinin (MODY) kliniği
ve gelişiminden sorumlu tanımlanmış mutasyonlar ve etkileri oldukça heterojendir.
Bu amaçla, çalışmamızda HNF1A gen
mutasyonları ile gelişen MODY3'te etken rs1169288 (c.79A>C, p.I27L)
yanlış anlamlı mutasyonunun hastalığın klinik ve biyokimyasal parametreleri
üzerine etkisinin incelenmesi hedeflenmiştir. Çalışmamızda 79 sağlıklı kontrol
ve 75 MODY ön tanılı hastada HNF1A rs1169288 mutasyonu yeni nesil
dizileme (NGS) ile incelenmiş ve mutasyonun klinik ve laboratuvar
parametrelerle ilişkisi SPSS(20.0) istatistik programıyla araştırılmıştır. HNF1A rs1169288
(A>C) mutasyonu genotiplerinin kontrol grubundaki etkileri
incelendiğinde mutant-CC genotipi taşıyan bireylerde A alleli taşıyanlara
kıyasla Gama glutamil transferaz (GGT) ve Hemoglobin (Hb) düzeylerinin (p=0,014;
p=0,027) yüksek; hasta grubunda ise, CC genotipi taşıyanlarda normal A alleli
taşıyanlara kıyasla başvuru kan şekerinin (BKŞ) yüksek (p=0,016) ve üre
düzeyinin düşük (p=0,022) olduğu gözlenmiştir (307,86±28,11 vs 175,65±25,59). Ancak
bu genotipin diğer klinik ve biyokimyasal parametreler üzerine anlamlı bir etkisi
gözlenmemiştir (p>0.05). Literatür çalışmaları yaygın MODY formlarından biri
olan MODY3 için hastalığın klinik tanısını kolaylaştıracak yeterli ayırt edici
parametre olmadığı yönündedir. Bu anlamda çalışmamız hastalığın klinik ve
biyokimyasal bulgularının anlamlandırılmasına katkı sağlamakta ve MODY
kliniğinde HNF1A rs1169288 mutasyonunun serum GGT, Hb, BKŞ ve üre düzeylerinde
etkili olabileceğine dikkat çekmektedir.

Keywords

MODY, HNF1A, rs1169288

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