Tip 2 Diyabet Mellitus Hastalarında FTO ve PPARG Genlerinin Metilasyon Profillerinin Belirlenmesi

Year 2024, Volume: 11 Issue: 3, 173 - 179, 18.12.2024

Menderes Yusuf Terzi , Meral Urhan Küçük , Müge Özsan Yılmaz , Zehra İlçe Kaya

https://doi.org/10.47572/muskutd.1523669

Abstract

Tip 2 diyabet (T2DM), genetik yatkınlıklar, çevresel etkileşimler ve çeşitli genler tarafından yönlendirilen karmaşık bir metabolik hastalıktır. Günümüzde, giderek artan sayıda çalışma diyabetes mellitus (DM) ile epigenetik, özellikle DNA metilasyonu arasındaki ilişkiyi göstermektedir. Bu çalışmada, klinik olarak T2DM tanısı almış hastaların periferik kan örneklerinde yağ kütlesi ve obezite ilişkili (FTO) ve peroksizom proliferatör aktive reseptör gama (PPARG) metilasyon düzeylerini ölçmeyi amaçladık. Çalışmamızda, Endokrinoloji Polikliniğine başvuran T2DM hastalarından (n=43) ve yaş-cinsiyet eşleştirilmiş sağlıklı bireylerden (n=42) tam kan alındı. Tam kan örneklerinden izole edilen genomik DNA'ların bisülfit dönüşümünden sonra hedef genlerin metilasyon profilleri metil-spesifik PCR ve jel elektroforezi yöntemleri ile analiz edildi. İstatistiksel analizler sonrası, T2DM ve kontrol grupları arasında FTO metilasyon durumu açısından anlamlı bir fark bulunmadı. T2DM'de PPARG geninin metilasyon seviyesi kontrol grubuna kıyasla önemli ölçüde daha yüksekti. PPARG'nın insülin duyarlılığını artırıcı etkileri göz önüne alındığında, bulgularımız metilasyon aracılı PPARG gen ekspresyonunun baskılanmasının T2DM hastalarında insülin direncinin yükselmesine yol açabileceği olasılığını doğrulamaktadır. T2DM hastalarında PPARG genindeki metilasyonun etkilerini ve hastalıkla ilişkisini daha iyi anlamak için daha fazla hasta ve kantitatif yöntemlerle yürütülen daha fazla gen ekspresyonu çalışması gerekecektir.

Keywords

DNA Metilasyonu, FTO, PPARG, Tip 2 Diabetes Mellitus

Project Number

22.GAP.061

The Identification of Methylation Profiles of FTO and PPARG Genes in Type 2 Diabetes Mellitus Patients

Abstract

Type 2 diabetes (T2DM) is a complex, metabolic disease driven by genetic susceptibilities, environmental interactions, and various genes. Nowadays, increasing number of studies show the relationship between diabetes mellitus (DM) and epigenetics, especially DNA methylation. In this study, we aimed to measure the methylation levels of fat mass and obesity associated (FTO) and peroxisome proliferator activated receptor gamma (PPARG) in the peripheral blood samples of patients with clinical diagnosis of T2DM. In our study, whole blood was taken from T2DM patients (n=43) who applied to the Endocrinology Outpatient Clinic and from age-gender-matched healthy individuals (n=42). After the bisulfide conversion of isolated genomic DNAs from whole blood samples, the methylation profiles of target genes were analyzed with methyl-specific PCR and gel electrophoresis methods. Post-statistical analyses, no significant difference was found between the T2DM and control groups regarding FTO methylation status. The methylation level of PPARG gene in T2DM was significantly higher compared to the control group. Given the insulin sensitizing effects of PPARG, our findings confirm the possibility that methylation-mediated suppression of PPARG gene expression may lead to elevation of insulin resistance in T2DM patients. Further gene expression studies with more patients and quantitative methods will be required to better understand the effects of methylation in the PPARG gene in T2DM patients and its relationship to the disease.

Keywords

DNA Methylation, FTO, PPARG, Type 2 Diabetes Mellitus

Ethical Statement

The present study was approved by Hatay Mustafa Kemal University Clinical Research Ethical Board (Date: 06/09/2021, issue No: 4298783/05045).

Supporting Institution

Scientific Research Projects Unit in Hatay Mustafa Kemal University

Project Number

22.GAP.061

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