MMP9 Geninin Aort Diseksiyonundaki Olası Etkilerinin Araştırılması

Year 2021, Volume: 11 Issue: 1, 12 - 20, 03.05.2021

Burcu Salman Yaylaz Melda Sarıman Ahmet Ekmekçi Emel Ergül Mahmut Uluganyan Fulya Coşan Özgün Melike Totuk Gedar Neslihan Abacı

https://doi.org/10.26650/experimed.2021.874159

Abstract

Amaç: Kardiyovasküler hastalıklar ve kanser metastazında sıklıkla araştı-rılan matriks metalloproteinazlar (MMPs) ekstraselüler matriks düzenle-yicileridir. Çalışmamız, aort diseksiyonu olan hastalarda MMP9 genindeki spesifik polimorfizmleri incelemeyi ve MMP9'un aort diseksiyonu üzerin-deki etkisini ekspresyon veri setleri ile karşılaştırmayı amaçlamaktadır.

Gereç ve Yöntem: Q279R ve P574R polimorfizmleri 44 aort diseksiyon tanısı almış ve 40 sağlıklı bireyde polimeraz zincir reaksiyonu - restrik-siyon parça uzunluğu polimorfizmi (PCR-RFLP) yöntemiyle çalışıldı. Q279R ve P574R prevalansı istatistiksel olarak hastaların tıbbi verileriyle karşılaştırıldı. Buna ek olarak, NCBI GEO veri tabanından aort diseksiyon veri setleri toplandı ve MMP9 ifadesindeki farklılıkları görmek amacıyla bu veri setleri GEO2R ve RStudio ile yeniden analiz edildi. Elde edilen sonuçların informatik analizi için çevrimiçi veri tabanları kullanıldı.

Bulgular: CG alleli taşıyıcısı kadınların aort diseksiyonu geliştirme riski erkeklerden daha yüksek bulunmasına rağmen her iki çalışma grubun-da da allellerin genotipik dağılımı benzer bulunmuştur. MMP9'un pro-tein-protein etkileşim analizinin ve hastaların tıbbi verilerinin incelen-mesinin sonucu olarak, P574R hipertansiyonu olan hastalarda önemli bir bulgu olarak değerlendirilmiştir. Array verisi analizinde ise MMP9 ifa-desinde kritik bir değişim gözlemlenmemiş olup, birçok örnekte TIMPifade seviyelerinde azalma tespit edilmiştir. Ayrıca MMP9’u hedefleyen miRNA ekspresyon seviyelerinin aort dokusu ve kanda düşük olduğu saptanmıştır.

Sonuç: Q279R ve P574R, MMP9 protein yapısını doğrudan etkilemeyen iki polimorfizmdir. İncelenen polimorfizmler ve gerçekleştirilen meta-a-nalizler, MMP9'un fenotipi doğrudan etkilemediği, ancak istatistiksel sonuçlarda görüldüğü gibi aort diseksiyonu gelişimi için zemin hazır-ladığını göstermektedir.

Keywords

Aort diseksiyon, MMP9, Q279R, P574R, gen ifade verisi

Supporting Institution

İstanbul Üniversitesi Bilimsel Araştırma Projeleri Birimi

Project Number

23468

A Brief Reconnoitre about Effects of MMP9 on Aortic Dissection

Abstract

Objective: Matrix metalloproteinases (MMPs) are the extracellular ma-trix regulators that frequently investigate cardiovascular diseases and cancer metastasis. Our study aimed to examine specific polymorphisms in the MMP9 gene in our patients with aortic dissection and compare the effect of MMP9 on aortic dissection with expression datasets.

Materials and Methods: Q279R and P574R polymorphisms were analyzed in 44 aortic dissection patients and 40 healthy donors via polymerase chain reaction-restriction fragment length polymorphism. (PCR-RFLP) methods. Q279R and P574R prevalence was statistically compared with the medical data of the patients. Additionally, we col-lected datasets of aortic dissection from NCBI GEO to reanalyze GEO2R and RStudio to see metalloproteinase activity on samples. Later, enrich-ment analysis was processed on widely used databases.

Results: Genotypic distribution of alleles was similar in the two study groups. In addition to this, female CG carriers had a higher risk of de-veloping aortic dissection than those of males. As the results of the protein-protein interaction analysis of MMP9 and patients’ clinical data, hypertension was found to be the significant outcome of P574R varia-tion in the patients. In array analysis, MMP9 expression did not change critically, but TIMPs had been downregulated in many samples. Also, MMP9 targeted miRNA expression levels were detected as low in aortic tissue and blood.

Conclusion: Q279R and P574R are two polymorphisms that do not di-rectly affect MMP9 protein structure. Consequently, studied polymor-phisms and performed meta-analysis show that MMP9 does not spark off the phenotype but sets the stage for aortic dissection development as seen in the statistical results. Furthermore, enrichment analysis on datasets shows MMP9 was not a primary reason for vascular remodeling.

Keywords

Aortic Dissection, MMP9, Q279R, P574R, Polymorphism, Gene Expression Data

Project Number

23468

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