title: The influence of three endothelin-1 polymorphisms on the progression of IgA nephropathy.
abstract: 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.
authors.affiliation: Department of Nephrology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic. ditama@centrum.cz
authors.forename: D
authors.initials: D
authors.lastname: Maixnerová
authors.forename: M
authors.initials: M
authors.lastname: Merta
authors.forename: J
authors.initials: J
authors.lastname: Reiterová
authors.forename: J
authors.initials: J
authors.lastname: Stekrová
authors.forename: R
authors.initials: R
authors.lastname: Rysavá
authors.forename: H
authors.initials: H
authors.lastname: Obeidová
authors.forename: O
authors.initials: O
authors.lastname: Viklický
authors.forename: P
authors.initials: P
authors.lastname: Potmĕsil
authors.forename: V
authors.initials: V
authors.lastname: Tesar
mesh_terms: D016022:Case-Control Studies; D018450:Disease Progression; D019332:Endothelin-1 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005922:Glomerulonephritis, IGA / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide
chemical_list: D019332:Endothelin-1