Analysis of DNA polymorphisms in the Endothelin-1 and Endothelin-A Receptor Genes in patients with hypertension

O. LASSEN, J. HERRERA, S. TABARES,A. GARUTTI, G. DOTTO, R. SOSA, R GALLERANO, A. SEMBAJ

Buenos Aires

Congreso; 29 th World Congress of Internal Medicine; 2008

Analysis of DNA polymorphisms in the Endothelin-1 and Endothelin-A Receptor Genes in patients with hypertension O. Lassen2, J. Herrera1, S. Tabares1,A. Garutti3, G. Dotto3, R. Sosa2, R Gallerano2, A. Sembaj1.1Biochemistry and Molecular Biology Department. School of Medicine, National University of Cordoba Unit of Internal Medicine Nº3. School of Medicine, National University of Cordoba, Cordoba Public Hospital 3Central Laboratory of Biochemistry, Cordoba Public Hospital Endothelin-1 (ET-1) is a potent vasoconstrictive peptide produced primarily by vascular endothelial cells. ET-1 may be a marker for arterial vascular disease; several studies showed an association between plasma endothelin level and a number of vascular diseases. The potent vasoconstrictor effect of ET-1 is predominantly mediated by the activation of ET receptors type A (EDNRA). The role of endothelin genes has been studied in the predisposition to myocardial infarction and in the development of hypertrophic cardiomyopathy. Actually, the ET-1 receptor and ET-1 ligand genes are polymorphic markers that allow the determination of the involvement of these gene variants in the cardiovascular disease. We described the frequencies of His323His (C/T) polymorphisms in EDNRA and 138A insertion/deletion (I/D) in ET-1 gene and the probable influence of these polymorphisms in patients with hypertension (HTA) and normotense population from Cordoba city. All subjects were provided with written informed consent to participate and the protocol has been approved by the ethics committee. We recluted 44 HTA patients attending the Cordoba Hospital and 40 healthy volunteer. Hypertension was defined as a systolic blood pressure (SBP) of 140 mmHg or higher and /or a diastolic blood pressure of 90 mmHg or higher. Blood samples were taken for routine clinical analysis. Genomic DNA was isolated from leukocytes and genotyped by a polymerase chain reaction–restriction fragment length polymorphism. The ET-1 gene, an adenine insertion (138 /ex1ins/delA) is a genetic variant associated with hypertension. The 4A/4A genotype was identified in 11.4% of HTA patients and in 40% of healthy subjects, a low frequency (25%) of the -4A allele was observed in HTA. The genotype -3A/-3A was present in 27.3% of HTA and 12.5% of controls. Our results are agreement with Dong Y. (2004, Hypertension 44; 884-890) that observed that the 138/ex1ins allele showed a modest correlation with low SBP. According to statistical analysis, an individual with the allele 3A is at risk to develop a cardiovascular affection. Further studies are being developed to know whether or not an association of these two polymorphisms with the clinical status of the patients exists.