title: Prediction of susceptible biomarkers for end stage renal disease among North Indians.
abstract: OBJECTIVE
  Involvement of pro-inflammatory genes has been correlated with basic kidney diseases and end stage renal disease (ESRD). However, results at odds were often noted from such independent association studies. This study proposes a genome wide analysis approach to predict ESRD risk associated genes.
  
  
  METHODS
  We included 42 single nucleotide polymorphisms (SNPs) showing association among north Indian ESRD cases and controls. ESRD cases comprised chronic glomerulonephritis (CGN), chronic interstitial nephritis (CIN), hypertension (HTN) and autosomal dominant polycystic kidney disease (ADPKD). Genotyping data obtained from our prior published reports were compared with Genome-Wide Association Studies (GWAS) SNPs retrieved from HapMap and GWASCentral databases using R-statistical package SNPAssoc. Linkage disequilibrium (LD), gene-gene interaction, classification and regression tree (CART) and pathway analysis were carried out in the present study supplemented with IL-6 and TNF-α levels estimation using enzyme linked immunosorbent assay (ELISA).
  
  
  RESULTS
  Comparison of genotyping data with GWAS SNPs revealed significant associations for interleukin (IL)1-RN, IL-6, MTHFR, tumour necrosis factor-α (TNF-α) and CCR3 genes with ESRD. Nine SNPs were commonly associated with CGN, CIN, HTN, ADPKD and ESRD. LD (D = 0.9) and gene-gene interaction (P = 0.0002) analyses revealed significant associations for IL-6 and TNF-α genes. In a consistent manner, CART analysis and functional analysis servers predict predisposing effects for TNF-α and IL-6 with ESRD. Finally, higher body circulating levels were observed for mutant TNF-α and IL-6 alleles among ESRD.
  
  
  CONCLUSIONS
  The study indicates significance for IL-6 and TNF-α gene with basic kidney diseases and ESRD. Extensive statistical tests, pathway analysis and functional assays also reflect attenuated level of significance for these SNPs. In future these may be brought from bench side to clinical practice as diagnostic biomarkers upon external and prospective replication and confirmation among other cohorts.
authors.affiliation: Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, India.
authors.forename: Swayam
authors.initials: S
authors.lastname: Prakash
authors.affiliation: Biomedical Informatics Centre, School of Telemedicine and Biomedical Informatics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, India.
authors.forename: Aditya Narayan
authors.initials: AN
authors.lastname: Sarangi
authors.affiliation: Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Tripathi
authors.affiliation: Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, India.
authors.forename: Raj Kumar
authors.initials: RK
authors.lastname: Sharma
authors.affiliation: Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, India.
authors.forename: Suraksha
authors.initials: S
authors.lastname: Agrawal
mesh_terms: D016022:Case-Control Studies; D019295:Computational Biology; D004252:DNA Mutational Analysis; D030541:Databases, Genetic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007194:India / Q000453:epidemiology; D018836:Inflammation Mediators / Q000097:blood; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics*
chemical_list: D005819:Genetic Markers; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha
keywords: end stage renal disease; genome wide analysis; interleukin-6; single nucleotide polymorphism; tumour necrosis factor-α