Ramanathan Gnanasambandan1, Ramprasad Elumalai2, Periyasamy Soundararajan2, Bhaskar V K S Lakkakula3,4. 1. Department of Biomedical Sciences, Sri Ramachandra University, Chennai, India. 2. Department of Nephrology, Sri Ramachandra University, Chennai, India. 3. Department of Biomedical Sciences, Sri Ramachandra University, Chennai, India. lvksbhaskar@gmail.com. 4. Genetic Lab, Department of Biochemistry, Sickle Cell Institute Chhattisgarh, Pt. JNM Medical College, Raipur, C.G., India. lvksbhaskar@gmail.com.
Abstract
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.
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 ADPKDpatients 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 AGTrs4762 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.
Authors: Vicente E Torres; Jared J Grantham; Arlene B Chapman; Michal Mrug; Kyongtae T Bae; Bernard F King; Louis H Wetzel; Diego Martin; Mark E Lockhart; William M Bennett; Marva Moxey-Mims; Kaleab Z Abebe; Yan Lin; James E Bost Journal: Clin J Am Soc Nephrol Date: 2010-11-18 Impact factor: 8.237
Authors: May E Montasser; Lawrence C Shimmin; Dongfeng Gu; Jing Chen; Charles Gu; Tanika N Kelly; Cashell E Jaquish; Treva K Rice; Dabeeru C Rao; Jie Cao; Jichun Chen; Paul K Whelton; Lotuce Lee Hamm; Jiang He; James E Hixson Journal: PLoS One Date: 2014-03-21 Impact factor: 3.240