The role of the biomarker and the genetic polymorphism of endothelin-1 in pulmonary arterial hypertension among Egyptians

Study objective: This study analyses for the first time endothelin-1 (ET-1) level, and gene polymorphisms for endothelin-1 (EDN1 gene) in patients with pulmonary arterial hypertension (PAH) in Egypt. Design: Cross-sectional study. Setting: Large, tertiary care, Alexandria university teaching hospital, Chest Department. Subjects: Thirty subjects with PAH with 30 control subjects. Methods: Subjects were divided into two groups of matched age and sex were allocated. The first group consisted of thirty subjects, ⩾18 years one group with no apparent evidence of disease free from pulmonary hypertension after full medical history, examination, and selected investigations (control group). The second group consisted of thirty subjects, ⩾18 years, suffering from pulmonary hypertension. All subjects who had a documented pulmonary hypertension with routine Echodoppler study were screened for endothelin-1(ET-1) and Gene polymorphism. Measurements and results: This study analyzed the frequency and the potential role of endothelin-1 and gene polymorphisms, the +134 del/insA, located in the gene encoding for endothelin-1 (EDN1) in PAH. Thirty patients with pulmonary hypertension (12 [40%] men) were included in the study (Table 1). The mean age of the patients was 53.5 ± 12.8 years range from 34 to 72 years. The two groups of patients and control subjects were matched as regard the age and gender. The endothelin-1 mean was 1.8 ± 1.3 fmol/ml with range from 0.3 to 3.8 fmol/ml in the patients group. The endothelin-1 mean was 0.7 ± 0.05 fmol/ml with range from 0.6 to 0.75 fmol/ml in the patients group. There was a significantly higher level of endothelin-1 in the group of pulmonary hypertension (p < 0.001). For the groups of polymorphisms studied, there was three genotypes (GT, TT, and GG), no substantial differences in genotype and allele distributions for +134 del/insA located in EDN1 gene, between PAH patients and control population, were observed (DF = 1; C.I. = 95.0; and p = 0.226). The genotype GG show the highest level of endothelin while the TT type show the lowest value of endothelin-1. Also, we found a significant relation between the higher endothelin-1 level and the lower oxygen saturation (p = 0.049), and the higher meanPAP (p = 0.004). Conclusions: In conclusion, our findings suggest a potential link between endothelin-1 level and specific genotypes in the EDN1 gene and susceptibility for PAH with a worse haemodynamic profile. Further investigations are warranted to understand the molecular basis and to confirm the potential clinical importance of these findings on larger cohorts of patients with PAH. This will impact on the management of PAH of Egyptian patients in the near future