Angiotensin-converting enzyme, angiotensin II receptor, apolipoprotein E and endothelial constitutive nitric oxide synthase gene polymorphisms in dilated cardiomyopathy
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Dosyalar
Tarih
2004
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Amaç: Dilate kardiyomiyopati (DCM) sol yada her iki ventrikülün sistolik fonksiyonlarının bozulması ve genişlemesi ile karakterize bir hastalıktır. Ailesel kökenli DCM'nin tanımlanmasından sonra ailesel olmayan DCM olguları için de genetik faktörlerin rol oynayabileceği düşünülmüş ve konuyla ilgili araştırmalar yapılmıştır. Makalemizde ülkemizde yaşayan DCM'li olgularda, hastalığın patofizyolojisinde rol oynaması muhtemel dört aday genin polimorfizmleri araştırılmıştır (Angiotensin dönüştürücü enzim (ACE) I/D polimorfizmi, angiotensin II reseptör (AGTR1) 1166 A/C polimorfizmi, apolipoprotein E (APOE) ve endotelyal konstitütif nitrik oksit sentaz (ecNOS) geni polimorfizmi). Ortalama yaşı 58±12 olan ardışık 76 hasta ve yaş ortalaması 59±12 olan 88 kontrol grubu çalışmaya alındı. Bütün hastalara ve kontrol grubuna ekokardiyografik çalışma yapıldı. DCM tanısı için ekokardiyografik olarak end-diastolik çapın >55mm ve ejeksiyon fraksiyonunun <%40 altında olması kriter alındı. Yine hasta grubuna koroner anjiografi yapılarak hastalar iskemik ve idyopatik DCM gruplarına ayrıldı. Spesifik kalp kası hastalığı, izole sağ ventrikül genişlemesi, kapak ve perikard hastalığı olanlar çalışma dışında tutuldu. Hasta ve kontrol grubunun kan hücrelerinden deoxiribonükleik asit (DNA) spesifik polimeraz zincir reaksiyonu (PCR) yöntemi ile genetik analiz yapıldı. Gen distribüsyonu ki kare testi ile değerlendirildi. Bağımsız risk için multivariate regresyon analizi uygulandı. 0,05 altındaki p değerleri istatistiksel olarak anlamlı kabul edildi. Sonuçlar: Hasta ve kontrol grubunun allel sıklıkları, ekokardiyografi, biyokimya analizi sonuçları ve demografik verileri karşılaştırıldı. APO E gen allel sıklığına ait dağılım her iki grupta farklılık gösterse de regresyon analizi sonuçlarına göre bu farklılığın bağımsız bir risk oluşturmadığı gözlendi.
Genetic factors are hypothesized to contribute to the dilated cardiomyopathy (DCM) susceptibility, even in sporadic cases. Abundant reports have investigated the association between various gene polymorphisms and the phenotypic expression of DCM. The aim of the present study is to assess the effect of four candidate gene polymorphisms (1166 A/C polymorphism of the angiotensin II type 1 receptor (AGTR1) gene, I/D polymorphism of angiotensin converting enzyme (ACE) gene, endothelial nitric oxide synthase (ec-NOS) and apolipoprotein E (APOE genes) on the pathogenesis of dilated cardiomyopathy. We studied 76 consecutive patients (mean age 58±12) with DCM and 88 healthy age- and sex-matched control subjects (mean age 59±12). All patients were assessed by 2-dimensional echocardiography and all had left ventricular dilatation (end diastolic diameter > 55 mm) and impaired systolic function (ejection fraction < 40%). All patients were catheterized. Patients having normal coronary arteries were classified as 'idiopathic' and the remaining group as 'ischemic' DCM. Patients with specific heart muscle disease, isolated right ventricular dilatation and valvular or pericardial disease were excluded. Deoxyribonucleic acid (DNA) was isolated from blood samples, and genotypes were determined by specific polymerase chain reaction (PCR) and separation of amplified fragments by agarose gel electrophoresis. We compared genotypes and allele frequencies, echocardiographic measurements, biochemical variables in our patients and control group. Age, sex, body mass index differences were statistically non-significant. APO E genotypes and allele frequencies were significantly different in patients with DCM. Multiple regression analyses demonstrated lack of independent association. Subgroup analysis revealed that the four candidate gene polymorphisms were not associated with ischemic or idiopathic DCM. Conclusions: No significant association exists between dilated cardiomyopathy and polymorphism of the AGTR1, ACE, ecNOS and APOE gene polymorphisms.
Genetic factors are hypothesized to contribute to the dilated cardiomyopathy (DCM) susceptibility, even in sporadic cases. Abundant reports have investigated the association between various gene polymorphisms and the phenotypic expression of DCM. The aim of the present study is to assess the effect of four candidate gene polymorphisms (1166 A/C polymorphism of the angiotensin II type 1 receptor (AGTR1) gene, I/D polymorphism of angiotensin converting enzyme (ACE) gene, endothelial nitric oxide synthase (ec-NOS) and apolipoprotein E (APOE genes) on the pathogenesis of dilated cardiomyopathy. We studied 76 consecutive patients (mean age 58±12) with DCM and 88 healthy age- and sex-matched control subjects (mean age 59±12). All patients were assessed by 2-dimensional echocardiography and all had left ventricular dilatation (end diastolic diameter > 55 mm) and impaired systolic function (ejection fraction < 40%). All patients were catheterized. Patients having normal coronary arteries were classified as 'idiopathic' and the remaining group as 'ischemic' DCM. Patients with specific heart muscle disease, isolated right ventricular dilatation and valvular or pericardial disease were excluded. Deoxyribonucleic acid (DNA) was isolated from blood samples, and genotypes were determined by specific polymerase chain reaction (PCR) and separation of amplified fragments by agarose gel electrophoresis. We compared genotypes and allele frequencies, echocardiographic measurements, biochemical variables in our patients and control group. Age, sex, body mass index differences were statistically non-significant. APO E genotypes and allele frequencies were significantly different in patients with DCM. Multiple regression analyses demonstrated lack of independent association. Subgroup analysis revealed that the four candidate gene polymorphisms were not associated with ischemic or idiopathic DCM. Conclusions: No significant association exists between dilated cardiomyopathy and polymorphism of the AGTR1, ACE, ecNOS and APOE gene polymorphisms.
Açıklama
Anahtar Kelimeler
AGTR1 Gene, ACE Gene, ecNOS Gene, APOE Gene, Polymorphism, Dilated Cardiomyopathy, AGTR1 Geni, ACE Geni, ecNOS Geni, APOE Geni, Polimorfizm, Dilate Kardiyomiyopati
Kaynak
Türk Kardiyoloji Derneği Arşivi
Archives of the Turkish Society of Cardiology
Archives of the Turkish Society of Cardiology
WoS Q Değeri
Scopus Q Değeri
Q4
Cilt
32
Sayı
5
