title: Interleukin-1 receptor antagonist gene polymorphism affects the progression of chronic renal failure.
abstract: End-stage renal disease (ESRD) involves an inflammatory process. Interleukin-1 receptor antagonist (IL-1Ra) and interleukin-1beta gene polymorphisms affect susceptibility to the disease in several inflammatory diseases. We investigated whether these polymorphisms are involved in ESRD by genotyping DNA from 602 dialyzed patients and 433 controls with polymerase chain reaction and digestion with restriction endonuclease. Allele 2 of the IL-1Ra VNTR polymorphism was associated with ESRD (OR=1.46, 95% CI 1.19-1.78). We also found a strong association between this allele and recurrent peritonitis in peritoneal dialysis patients. Odds ratio for the risk allele was higher compared to entire ESRD group (OR=3.6, 95% CI 1.70-7.44). The homozygosity for the allele 2 was associated with disease progression, especially in patients with diabetic nephropathy and glomerulonephritis. For the patients from these two subgroups having 2.2 genotype, the mean time from disease onset to ESRD was 1.5 and 2.2 years, respectively, compared to 6.4 and 9.8 years for those with 1.1 genotype. The IL-1Ra allele 2 is associated with ESRD in our dialyzed patients. Our results demonstrate for the first time the association of the IL-1Ra allele 2 with faster progression to ESRD. If confirmed in other populations, it might be a predictor of faster disease progression.
authors.affiliation: Laboratory for Molecular Diagnostics of Multifactorial Diseases, Department of Nephrology, University Medical School, Dr K. Jaczewskiego 8, 20-954 Lublin, Poland. monika.buraczynska@am.lublin.pl
authors.forename: Monika
authors.initials: M
authors.lastname: Buraczynska
authors.forename: Piotr
authors.initials: P
authors.lastname: Ksiazek
authors.forename: Piotr
authors.initials: P
authors.lastname: Kubit
authors.forename: Wojciech
authors.initials: W
authors.lastname: Zaluska
mesh_terms: D000328:Adult; D000367:Age Factors; D002784:Cholesterol / Q000097:blood; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood / Q000235:genetics*; D053583:Interleukin-1beta / Q000235:genetics; D007676:Kidney Failure, Chronic / Q000097:blood / Q000235:genetics* / Q000628:therapy; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D006435:Renal Dialysis; D012737:Sex Factors; D020080:Tandem Repeat Sequences / Q000235:genetics
chemical_list: C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D002784:Cholesterol