PKOS’lu Hastalarda INSR geni Ekzom Dizileme Sonuçları

Öz

Giriş ve Amaç: Polikistik over sendromu (PKOS), içerisinde insülin direnci, infertilite, hiperandrojenizm gibi bulgularının yer aldığı bir endokrinopatidir. Genetik alt yapısı çeşitli genlerde bulunan varyasyon ve mutasyonlarla araştırılmaya devam etmektedir. Gereç ve Yöntemler: Bu çalışmada AE-PKOS kriterlerine göre prospektif 16 PKOS hastasının klinik ve laboratuvar bulguları değerlendirip ve INSR geni ekzom dizileme yöntemi ile analiz ettik. Sonuçlar: Toplamda, 3 tanesini kendimizin isimlendirdiğimiz 4 novel varyasyonu ortaya çıkardık. Bunlar; NM_000208.4:c.974+82_974+83insT, NM_000208.4:c.974+107_974+108insC, NM_000208.4:c.653-79A>G ve rs1449625253 intronik varyasyonlarıdır. Toplamda 41 çeşit varyasyonu içeren 196 varyasyon ortaya çıkardık. INSR geninde bulduğumuz 27 bilgi verici SNP kullanılarak ilk kez bu çalışmada, yüksek linkaj eşitsizliği skoru (r2=1) gösteren 2 farklı üçerli tag SNP bloğunu saptadık. Bunlar; rs2963-rs2245649-rs2245655 ile rs6413502-rs41509747-rs73498780 bloklarıdır. Ayrıca, en sık görülen rs7508516 ve hastalarımızda da gözlemlediğimiz ve PKOS’dan sorumlu olabilecek rs2059807 gibi varyasyonların MAF değerlerini ortaya çıkardık. Tartışma: Çalışma Türkiye’de PKOS hastalarının INSR genlerinin ekzom dizileme yöntemi ile araştırıldığı ilk çalışmadır. INSR genine ait tag SNP’lerin ilk kez ortaya çıkarıldığı ve yeni aday varyasyonları bulduğumuz çalışma literatüre önemli veriler sunmaktadır.

Anahtar Kelimeler

• PKOS
• tag SNP
• INSR geni
• linkaj eşitsizliği
• ekzom dizileme

INSR gene Exome Sequencing Results in patients with PCOS

Öz

Objective: Polycystic ovary syndrome (PCOS) is an endocrinopathy that includes findings such as insulin resistance, infertility and hyperandrogenism. Its genetic background continues to be investigated with variations and mutations in various genes. Material and Methods: In current study, we evaluated the clinical and laboratory findings of 16 prospective PCOS patients according to AE-PCOS criteria and analyzed the INSR gene by exome sequencing method. Results: We revealed 4 novel variations, 3 of which we named ourselves. These are NM_000208.4:c.974+82_974+83insT, NM_000208.4:c.974+107_974+108insC, NM_000208.4:c.653-79A>G and rs1449625253 and are all intronic variations. In this study, using the 27 informative SNPs that we found in the INSR gene, we detected two different triple tag SNP blocks showing high linkage disequilibrium score (r2 = 1) for the first time. These blocks are rs2963-rs2245649-rs2245655 and rs6413502-rs41509747-rs73498780. We also revealed the MAF values of variations such as rs7508516, which is the most common, and rs2059807, which we observed in our patients and may be responsible for PCOS. Conclusion: The study is the first study in Turkiye in which the INSR genes of PCOS patients were investigated by exome sequencing method. The study, in which the tag SNPs of the INSR gene were revealed for the first time and we found new candidate variations, provides important data to the literature.

Anahtar Kelimeler

• PCOS
• tag SNP
• INSR gene
• linkage disequilibrium
• exome sequencing

Kaynakça

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