Angiotensinogen gene polymorphisms and progression of chronic kidney disease in ADPKD patients.
BACKGROUND
Autosomal dominant polycystic kidney disease (ADPKD) is a multisystemic and progressive disorder characterized by cyst formation and kidney enlargement and ultimately renal failure. Reduction of CKD progression in the ADPKD by pharmacological blockade of the renin-angiotensin-aldosterone system (RAAS) using ACE inhibitors indicated the involvement of RAAS pathway in the progression of CKD. The aim of the present study is to investigate the role of angiotensinogen tag-single nucleotide polymorphisms (AGT tag-SNPs) in progression of CKD.


METHODS
Twelve AGT tag-SNPs were genotyped in 102 ADPKD patients and 106 non-ADPKD subjects using FRET-based KASPar method. Genotypes and haplotypes were compared between ADPKD and controls. The effect of genotypes and hypertension on CKD progression was assessed using univariate and multivariate logistic regression. Mantel-Haenszel (M-H) stratified analysis was performed to study the interaction between CKD stages and hypertension.


RESULTS
Of the twelve tag-SNPs analyzed, only rs11122578 SNP deviated Hardy-Weinberg equilibrium in controls. Significant association between two AGT polymorphisms (rs11122577 and rs4762) and ADPKD was observed. Analysis of linkage disequilibrium revealed two haplotype blocks and haplotypes are not associated with ADPKD. The univariate analysis revealed that the age, hypertension, family history of diabetes and AGT rs4762 contributed to the progression of CKD in ADPKD. The modifier effect of these factors remained even after controlling other variables in multivariate analysis.


CONCLUSIONS
The results of our study suggest significant association between Thr207Met polymorphism of AGT and CKD progression and acts as an effect modifier of renal disease progression in ADPKD.
Department of Biomedical Sciences, Sri Ramachandra University, Chennai, India.
Ramanathan
R
Gnanasambandan
Department of Nephrology, Sri Ramachandra University, Chennai, India.
Ramprasad
R
Elumalai
Department of Nephrology, Sri Ramachandra University, Chennai, India.
Periyasamy
P
Soundararajan
Department of Biomedical Sciences, Sri Ramachandra University, Chennai, India. lvksbhaskar@gmail.com.|Genetic Lab, Department of Biochemistry, Sickle Cell Institute Chhattisgarh, Pt. JNM Medical College, Raipur, C.G., India. lvksbhaskar@gmail.com.
Bhaskar V K S
BVKS
Lakkakula
D000328:Adult; D000808:Angiotensinogen / Q000235:genetics*; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016891:Polycystic Kidney, Autosomal Dominant / Q000150:complications / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D051436:Renal Insufficiency, Chronic / Q000209:etiology*
D000808:Angiotensinogen
ADPKD; AGT gene; CKD; ESRD; Tag-SNP