Genetic polymorphisms of renin-angiotensin system and progression of interstitial nephritis.
Genes of the renin-angiotensin system (RAS) are involved in the progression of renal failure. Among them, the angiotensin-converting enzyme (ACE), angiotensinogen (AGT) and angiotensin II type 1 receptor (AT1R) genes are of particular interest. We examined polymorphisms of these three genes for association with the development of interstitial nephritis and progression to end-stage renal failure. The allele frequency and genotype distribution were compared in 90 patients with interstitial nephritis and 200 healthy controls. DNA samples were genotyped by polymerase chain reaction (PCR). We did not find statistically significant differences between groups in the insertion/deletion polymorphism of the ACE gene. An involvement of M235T polymorphism of the AGT gene in renal disease was observed in our study. The frequency of the T allele was higher in patients than in controls (32% vs. 24%). In the A1166C AT1R polymorphism the homozygous CC genotype was also more frequent in interstitial nephritis patients (7% vs. 3.5%). In patients carrying the C allele, an average time to ESRD was significantly shorter than in subjects with the AA genotype. Our study shows the association of the AGT and AT1R gene polymorphisms with the development and progression of interstitial nephritis. The C allele of the A1166C polymorphism appears to be a risk factor for faster disease progression.
Buraczyńska
Monika
M
Department of Nephrology, Medical University of Lublin.
Grzebalska
Agnieszka
A
Spasiewicz
Danuta
D
Orłowska
Grazyna
G
Ksiazek
Andrzej
A
D000328:Adult; D000803:Angiotensin I / Q000235:genetics; D000808:Angiotensinogen / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009395:Nephritis, Interstitial / Q000150:complications* / Q000235:genetics*; D011110:Polymorphism, Genetic; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics*; D018570:Risk Assessment / Q000379:methods; D013223:Statistics as Topic
D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen; D000803:Angiotensin I