Lipoprotein a ve gen polimorfizmi ile aort kapak kalsifikasyonu arasındaki ilişki
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Dosyalar
Tarih
2017
Yazarlar
Dergi Başlığı
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Yayıncı
Trakya Üniversitesi Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Kalsifik aort darlığı (KAD), multifaktöriyel bir hastalık olup hem çevresel hem de genetik faktörler etiyolojisinde önemli rol oynamaktadır. KAD'ın patogenezine katkıda bulunan aday genleri çalışmak, koroner arter hastalığı' nın etiyolojisinin anlaşılmasına yardımcı olabilir. Lipoprotein a [Lip (a)] yapısal olarak plazminojen ve doku plazminojen aktivatöre benzerlik gösteren ve plazminojenle bağlanma bölgesi için yarışma gösteren bir yapıya sahiptir. Bu yapısı nedeniyle fibrinolizi azaltma eğilimindedir. Ayrıca PAI-1 (plazminojen aktivatör inhibitör-1) sekresyonunu arttırdığı için trombojeniteyi ve yapısındaki kolesterol molekülü nedeniyle de aterogenezi artırır. Bunların yanı sıra daha fazla aterojenik olan oksidize fosfolipidleri taşıdığı için iltihabi döngüde rol alan inflamatuar hücrelerin bulunduğu bölgeye hücum etmesine ve bu bölgede düz kas hücrelerinde hücre proliferasyonuna neden olur. Bu durum Lip (a)'yı koroner arter hastalığı, inme, ateroskleroz ve kardiyovasküler hastalıklar için risk faktörü haline getirmiştir. Lip (a) gen polimorfizmlerin araştırılması, gen modülasyon tedavilerinin ilerleme gösterdiği günümüzde risk oluşturduğu hasta gruplarında tedavi olabileceği gibi bu polimorfizmleri taşıyan bireylerde erken tanı ve tedavi için bir umut olabileceği düşünülmüştür. Bu amaçla hastanemize başvurmuş semptom sonrası yapılan ekokardiyografi ile tanı almış KAD saptanan 75 hasta ve normal aort kapak saptanan kontrol grubundan 77 hastadan 5cc kan örneği alınarak Lip (a) düzeyi ve gen polimorfizmlerinin kalsifik aort darlığı ile ilişkili olup olmadıkları araştırılmıştır. Ekokardiyografi yapılan hastalarda açlık rutin kan tetkikleri laboratuvarımızda çalışılarak risk faktörleri açısından değerlendirilmiştir. Lip (a) düzeyi, rs10455872 polimorfizmi AA genotipi ve rs3798220 polimorfizmi TT genotipinin KAD gelişiminde genetik bir risk faktörü olduğu saptandı. Ayrıca sigara içiciliği, LDL yüksekliği, kreatinin yüksekliği (dolayısıyla düşük renal fonksiyonun) ve albümin düzeyi düşüklüğünün (muhtemel negatif akut faz reaktanı olarak) KAD gelişiminde risk faktörü olduğu tespit edilmiştir.
Calsific aortic valve disease (CAD) , as a multifactorial illness, has an important role in its environmental and also genetical etiology. By studying the probably suspicious genes that contributes pathogenesis of calsific aortic valve disease, etiology of CAD can be explained clearly. The structure of lipoprotein a [Lp(a)] is similar to plasminogen and tPA (tissue plasminogen activator) and it competes with plasminogen for its binding site, leading to reduced fibrinolysis. Also, because Lp(a) stimulates secretion of PAI-1, it leads to thrombogenesis. Lp(a) also carries cholesterol and thus contributes to atherosclerosis. In addition, Lp(a) transports the more atherogenic proinflammatory oxidized phospholipids, which attract inflammatory cells to vessel walls, and leads to smooth muscle cell proliferation. This stiation is became a risk factor high Lp(a) in blood for coronary heart disease (CHD), atherosclerosis, thrombosis, and stroke. The search for Lp(a) gene polymorphisms has been thought to be an option for early diagnosis and treatment of individuals carrying these polymorphisms as well as treatment in patients at risk for gene therapy modalities nowadays. For this purpose, we investigated Lp(a) level and gene polymorphisms were associated with calcific aortic stenosis by taking 5cc blood samples after echocardiography from 75 patients who had calcific aortic stenosis diagnosed and 77 patients with normal aortic valve. Before echocardiography, fasting blood tests were studied in our laboratory and evaluated and checked for risk factors. Lp(a) level, rs10455872 polymorphism AA genotype and rs3798220 polymorphic TT genotype were found to be a genetic risk factor in the development of calcific aortic stenosis. It has also been found that smoking, blood serum LDL level elevation, elevated creatinine (hence low renal function) and low albumin level (as a possible negative acute phase reactant) are risk factors for the development of calcified aortic stenosis.
Calsific aortic valve disease (CAD) , as a multifactorial illness, has an important role in its environmental and also genetical etiology. By studying the probably suspicious genes that contributes pathogenesis of calsific aortic valve disease, etiology of CAD can be explained clearly. The structure of lipoprotein a [Lp(a)] is similar to plasminogen and tPA (tissue plasminogen activator) and it competes with plasminogen for its binding site, leading to reduced fibrinolysis. Also, because Lp(a) stimulates secretion of PAI-1, it leads to thrombogenesis. Lp(a) also carries cholesterol and thus contributes to atherosclerosis. In addition, Lp(a) transports the more atherogenic proinflammatory oxidized phospholipids, which attract inflammatory cells to vessel walls, and leads to smooth muscle cell proliferation. This stiation is became a risk factor high Lp(a) in blood for coronary heart disease (CHD), atherosclerosis, thrombosis, and stroke. The search for Lp(a) gene polymorphisms has been thought to be an option for early diagnosis and treatment of individuals carrying these polymorphisms as well as treatment in patients at risk for gene therapy modalities nowadays. For this purpose, we investigated Lp(a) level and gene polymorphisms were associated with calcific aortic stenosis by taking 5cc blood samples after echocardiography from 75 patients who had calcific aortic stenosis diagnosed and 77 patients with normal aortic valve. Before echocardiography, fasting blood tests were studied in our laboratory and evaluated and checked for risk factors. Lp(a) level, rs10455872 polymorphism AA genotype and rs3798220 polymorphic TT genotype were found to be a genetic risk factor in the development of calcific aortic stenosis. It has also been found that smoking, blood serum LDL level elevation, elevated creatinine (hence low renal function) and low albumin level (as a possible negative acute phase reactant) are risk factors for the development of calcified aortic stenosis.
