The influence of three endothelin-1 polymorphisms on the progression of IgA nephropathy.

The clinical course of chronic renal diseases and their progression to ESRF is highly variable. Different candidate gene polymorphisms have been advocated as possible modulators of ESRF progression. Moreover, ET-1 has been suggested as a major promoting factor in renal disease. However, limited data are available regarding an association of three ET-1 SNP K198N, T- 1370G and 3A/4A with the progression of IgAN to ESRF. We examined a group of 122 pts with histologically proved IgAN (91 pts with normal renal function, 31 pts with ESRF), as a control group we used 132 genetically unrelated healthy subjects. Patients' DNAs were genotyped for three ET-1 SNP: K198N, T-1370G and 3A/4A by means of PCR. The frequencies of different genotypes and ET-1 gene haplotypes were compared among control group, IgAN pts with normal renal function and IgAN pts with ESRF. The ET-1 genotype distribution showed no differences among the groups of IgAN with normal renal function (1. K198N - 63.74% KK, 32.97% KN, 3.3% NN; 2. TT - 68.13% TT, 28.57% TG, 3.3% GG; 3. 3A/4A - 42.22% 3A/3A, 50.0% 3A/4A, 7.69% 4A/4A ), IgAN with ESRF (1. K198N - 74.19% KK, 25.81% KN, 0% NN; 2. TT - 77.42% TT, 22.58% TG, 0% GG, 3. 3A/4A - 56.25% 3A/3A, 37.5% 3A/4A, 6.25% 4A/4A ) and the control group (1. K198N - 66.67% KK, 31.82% KN, 1.52% NN, 2. TT - 76.51% TT, 22.72% TG, 0.76% GG, 3. 3A/4A - 43.94% 3A/3A, 44.70% 3A/4A, 11.36% 4A/4A ). The analysis of haplotypes showed that the frequency of G-198, G-1370 and 4A allele combination was significantly higher in comparison with the control group (P=0.0056). We excluded the effect of K198N, T-1370G and 3A/4A polymorphisms of the ET-1 gene in single-gene analysis on the progression of IgAN to ESRF. A significant association of the GG4A haplotype with IgAN, demonstrated by haplotype reconstruction of the ET-1 gene, could suggest a role in the pathogenesis of IgAN.