The aim was to investigate the frequency distribution of the common polymporphism of the endothelin (ET-1) gene and its possible relation regarding hemodynamical consequence of malignant ventricular arrhythmias in patients with structural heart disease. We studied 26 consecutive pts with malignant ventricular arrhythmias and implantable cardioverter-defibrillators (ICD) in mean age 62,7+-12,2 years and mean left ventricular ejection fraction LVEF 0.37+-41. Taq polymorphism of ET-1 was detected using our original PCR method. Of 26 patients: 9(34%) had reccurent palpitations and 8 (30.8%) had syncopes during their malignant arrhythmias. 19 pts received after ICD implantation amiodarone, 7 were not. 15 pts had (++), 11 (+-) and 0 (--) ET-1 genotype. The risk for syncopes was associated with (++) genotype of the ET-I gene (p=0.01). Patients with amiodarone had significantly higher frequency of the (++) genotype (p=0.011).

The object of the study was to investigate the share of the polymorphisms I/D ACE, endothelin 1 4127G/A and TNF-β NcoI in the susceptibility to proliferative diabetic retinopathy (PDR) in non-insulin-dependent diabetes mellitus (NIDDM). Genotypes were detected by polymerase chain reactions and determined in a set of 246 Caucasian NIDDM subjects with defined PDR status. The relevance of genotypes and clinical characteristics to the PDR occurrence was tested using multiple linear regression models and discrimination analysis. The best predictive value for PDR was given by a combination of two parameters – NIDDM duration and the TNF-β genotype (p < 1·10–6 and p = 1·10–2, respectively) with a correct retrograde prediction of 82.6%. A comparison of the TNF-β NcoI allele frequencies revealed no difference between NIDDM and nondiabetic subjects (n = 176), but a statistically significant difference was found between PDR and non-PDR NIDDM subjects (after a correction for the number of comparisons p = 0.03), allele β2 being associated with PDR. Our results identified the allele variant TNF-β2 being associated with PDR in NIDDM. Diabetes duration and the TNF-β NcoI genotype were proven to significantly predict PDR occurrence. The TNF-β2 allele could be regarded as a separate genetic risk factor that increases the relative incidence of PDR in patients with NIDDM.

Four hundred of Caucasian (Czech) normotensive (normotension was confirmed by 24-h ambulatory blood pressure monitoring) and hypertensive subjects of the age of 45-55 years were compared in three ET-1 gene (6p21.3) polymorphisms CA/CT dinucleotide repeat in Z-area, I/D (-4A/-3A) polymorphism in the promoter and Taq1 (G8002A) polymorphism in the intron 4 detected by PCR methods.The allelic length of CA/CT dinucleotide repeat polymorphism was significantly higher in hypertensive subjects (P=0.032). Allelic concurrence of I/D promoter polymorphism and Taq1 polymorphism was significantly different (P=0.008) in hypertensive vs.normotensive women (not in men). Linkage disequilibria between CA/CT and Taq polymorphisms were found both in hypertensive (P=0.008) and normotensive (P=0.02) subjects. Complex interaction among alleles inside the gene coding for ET-1 gene could participate in pathogenesis of essential hypertension.