Arzu ERGEN, Oğuz ÖZTÜRK, Ümit ZEYBEK, Bedia AĞAÇHAN, Soner TATLIDEDE, Ercan ÇAKMAK, Gürsel TURGUT, Arzu ÖZCAN, Lütfü BAŞ

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Paraoxonase-1 192 enzyme polymorphism in non-syndromic clefting: in patients and parents

Orofasyal yarıkların büyük çoğunluğu genellikle nonsendromiktir ve iki farklı gruba ayrılabilir: yarık damak ile birlikte veya olmaksızın yarık dudak ve sadece yarık damak. Her ikisinin de genetik komponentleri oldukça karmaşıktır, ayrıca çevresel faktörler de palatogenezde etkilidir ve bir genin veya lokusun izole edilmesi oldukça zordur. Özellikle epitelyal- mezenkim transformasyonu damak bütünlüğünün sağlanmasında kritik bir olaydır. Damak formasyonunda, apoptoz birbirine karşılıklı gelen epitelin düzgün damak yapısını oluşturmasını sağlamak için yapışmayı ve dokunmayı artırır. Apoptoz, vücutta gelişim sırasında organelleri şekillendirmek için önemlidir. Damak formasyonunda oksidatif stresin epitelyal apoptoza neden olabileceğini ileri sürmekteyiz. Reaktif oksijen ürünlerinin üretimi ile ve hücre içi antioksidatif enzimlerin ve hücre dışı antioksidatif mekanizmaların aşılması ile oksidatif stres meydana gelir. Aşırı oksidatif stres hücrede peroksidatif hasar oluşturur ve hücre fonksiyonunu değiştirerek patolojik etkilere neden olur. Paraoksonaz enzimi antioksidatif mekanizmada etkili bir serum enzimidir. Bu çalışmamızda oksidatif stres ve yarık dudak/damak palatogenezinde ilişkisini ve bu süreçte paraoksonaz gen polimorfizminin rolünü açıklamayı amaçladık. Bu çalışmaya dahil edilen vakalar Şişli Etfal Eğitim ve Araştırma Hastanesi Plastik, Rekonstrüktif ve Cerrahi Kliniğine Ağustos 2004 ile Ocak 2006 arasında başvuran hastaların tıbbi kayıtlarından alındı. 50 sendromik olmayan yarık dudak ve damaklı hasta ve aileleri incelendi. Kan örnekleri EDTA’lı tüplere alındıktan sonra DNA, lökositlerin SDA amonyum asetat lizisi ile ekstraksiyonu ve etanol presipitasyonu ile hazırlandı. PON1 genotipleri daha önce yayınlanmış protokollere göre PCR uygulamasını takiben belirlendi. Furlong (1989) tarafından uygulanan yönteme göre serumda Paraoksonaz aktivitesi araştırıldı. Sendromik olmayan yarık dudak ve damaklı hastalarda ve kontrol gruplarında PON-1 192 gen polimorfizminin sıklığını araştırdık.

Sendromik olmayan yarık damak ve dudaklı hasta ve ailelerinde paraoksonaz-1 192 enzim polimorfizmi

Most orofacial clefts are nonsyndromic, isolated defects, and are classified into two groups: cleft lip (CL) with or without cleft palate and cleft palate (CP) only. Both are genetically complex traits, the genetic cause is stil elusive, it is genetically complex and enviromental factors are also responsible for the pathogenesis. Epithelial transformation to mesenchyme is an important event during the process of palatogenesis. Specifically, epithelial-mesenchymal transformation is thought to be critical for the disappearance of the seam and mesenchymal confluence. In palate formation, apoptosis is thought to facilitate adherence, or touching, of the opposing epithelium to form a seam. Apoptosis is important to sculpt the organelles in the body during development. We hypothesize that oxidative stress promotes epithelial cell apoptosis during palate formation. Oxidative stress occurs when the production of reactive oxygen species (ROS), including free radicals, exceeds the handling capability of intracellular antioxidant enzymes and extracellular antioxidant defenses. Excessive oxidative stress leads to peroxidative damage to cells, altered cellular function, and pathologic effects. Paraoxonase (PON) is a serum enzyme that is associated with antioxidant mechanism. We aim to determine the prevalance of the PON-1 192 polymorphisms in the patients and control groups. All cases included in this study are from the medical records of the Plastic, Reconstructive and Esthetic Clinic of Sisli Etfal Research and Training Hospital from August 2004 to January 2006. 50 nonsyndromic CL and CP cases and parent were analyzed. Blood specimens were collected in tubes containing EDTA, and DNA was prepared from leucoycte pellet by SDS lysis ammonium acetate extraction and ethanol precipitation. PON-1 genotypes were determined following PCR according to previously published protocols. Paraoxonase activities was measured according to Furlong et al. (1989). We evaluated the frequencies of polymorphisms of the PON1-192 gene in nonsyndromic cleft lip and cleft palate patients and in matched control subjects.
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Journal of Cell and Molecular Biology-Cover
  • ISSN: 1303-3646
  • Yayın Aralığı: Yılda 2 Sayı
  • Yayıncı: Haliç Üniv. Fen Edebiyat Fak.
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Paraoxonase-1 192 enzyme polymorphism in non-syndromic clefting: in patients and parents

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