Relationship between the A(8002)G intronic polymorphism of pre-pro-endothelin-1 gene and the endothelin-1 concentration among Tunisian coronary patients

Abstract

Background: Acute coronary syndromes (ACS) are complex and polygenic diseases which are a real problem of public health. These syndromes require multidisciplinary studies to understand the pathogenesis mechanisms. Our study aims to evaluate the endothelin-1 (ET-1) serum concentration in Tunisian coronary compared to controls healthy, as well as the study of the impact of an intronic polymorphism A (8002) G of pre-pro-endothelin-1 Gene (inactive precursor of ET-1) on the change in serum endothelin-1 and in the susceptibility to Acute coronary syndrome (SCA). Methods: Our samples were subdivided into coronary patients (157) and healthy subjects (142). The quantification of the ET-1 concentration was performed by high performance liquid chromatography, the identification of the different genotypes of the polymorphism A(8002)G was made by PCR-RFLP. The association between the ET-1 concentration and identified genotypes was realized by adapted software for descriptive statistics, Statistical Package for the Sociological Sciences (SPSS v 21.0). Results: Our study showed that the concentration of ET-1 was significantly higher in patients compared to controls and that the mutated allele prevails in patients F (G) = 0.78 and there is a minority in controls F (G) = 0.3. Secondly the homozygous genotype GG is associated with higher concentrations of ET-1 in patients and controls, heterozygous genotype AG is associated with intermediaries' values and AA genotype is related to lower values. Conclusion: Although the polymorphism studied is an intronic polymorphism, it is involved in the change in serum concentration of ET-1 and is a candidate gene in susceptibility to SCA. Cardiovascular diseases are "polygenic" pathology and do not obey of the law for transmission of Mendel.