title: Renin gene rs1464816 polymorphism contributes to chronic kidney disease progression in ADPKD.
abstract: BACKGROUND
  Autosomal dominant polycystic kidney disease (ADPKD) is a monogenic disorder and is a common genetic cause of chronic renal failure in children and adults. The enzyme renin plays a key role in the RAAS cascade and an important role in the development of hypertension and progression of renal disease in ADPKD. The present study is aimed to investigate the potential modifier effect of REN gene polymorphisms on the progression of chronic kidney disease (CKD) in ADPKD.
  
  
  METHODS
  We analyzed 102 ADPKD patients and 106 healthy controls from the same geographic area. FRET-based KASPar single-nucleotide polymorphism (SNP) genotyping assays for REN gene tag-SNPs (rs2887284, rs2368564, rs1464816, rs7521667, rs10900555, rs6693954, rs6676670 and rs11571078) were performed. Cochran-Armitage trend test was used to assess the potential associations between these polymorphisms and CKD stages. Haplotype frequencies and LD measures were estimated by using the software Haploview. Mantel-Haenszel stratified analysis was used to explore confounding and interaction effects of these polymorphisms.
  
  
  RESULTS
  Of the eight tag-SNPs genotyped, the rs10900555 polymorphism deviated from the Hardy-Weinberg equilibrium in controls. The presence of ADPKD in general was not significantly associated with the REN tag-SNPs included in this study. Linkage disequilibrium analysis yielded three haplotype blocks and the haplotypes of the respective blocks are not statistically different between ADPKD and controls. In multivariate analysis, the rs1464816 TG genotype showed a significant association with the advancement of CKD in ADPKD (OR = 4.80; 95 % CI = 1.30-17.82; p = 0.019).
  
  
  CONCLUSIONS
  The present study provides evidence that the rs1464816 polymorphism in REN is associated with CKD progression in ADPKD.
authors.affiliation: Department of Biomedical Sciences, Sri Ramachandra University, Chennai, India. Gnans05@gmail.com.
authors.forename: Gnanasambandan
authors.initials: G
authors.lastname: Ramanathan
authors.affiliation: Department of Nephrology, Sri Ramachandra University, Chennai, India. ramprasadnephro@gmail.com.
authors.forename: Ramprasad
authors.initials: R
authors.lastname: Elumalai
authors.affiliation: Department of Nephrology, Sri Ramachandra University, Chennai, India. srajan_51@hotmail.com.
authors.forename: Soundararajan
authors.initials: S
authors.lastname: Periyasamy
authors.affiliation: Department of Biomedical Sciences, Sri Ramachandra University, Chennai, India. bhaskar@scic.co.in.|Genetic Lab, Department of Biochemistry, Sickle Cell Institute Chhattisgarh, Pt. JNM Medical College, Raipur, 492001, CG, India. bhaskar@scic.co.in.
authors.forename: Bhaskar V K S
authors.initials: BV
authors.lastname: Lakkakula
mesh_terms: D000328:Adult; D000368:Aged; D002908:Chronic Disease; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012083:Renin / Q000235:genetics*
chemical_list: D012083:Renin