title: Association of chemokine gene variants with end stage renal disease in North Indian population.
abstract: OBJECTIVE
  The progression rate of chronic kidney disease (CKD) to its end-stage renal disease (ESRD), and the development and severity of various complications, are indirectly influenced by genetic and epigenetic factors. Chemokines are small inducible pro-inflammatory cytokines, which are implicated in many biological processes like migration of leukocytes, angiogenesis, tumor growth and metastasis. We tested association of four single nucleotide polymorphisms (SNPs) viz. CCL2I/D, CCL2A2518G, CXCL12G801A and CXCR2(+1208)C/T among individuals with ESRD (end stage renal disease) and normal healthy controls from North Indian population.
  
  
  METHODS
  CCL2I/D, CCL2A2518G, CXCL12G801A and CXCR2(+1208)C/T were genotyped in blood samples of hospital-based case-control study comprising of 200 ESRD cases and 200 healthy controls using Restriction Fragment Length Polymorphism (RFLP) and ARMS (Amplification Refractory Mutation Specific) PCR methodology.
  
  
  RESULTS
  A significant association was found in CXCL12G801A with ESRD risk. In case of CXCL12G801A polymorphism heterozygous (GA) genotype showed significant risk (p=0.039; OR=1.55) whereas A allele carrier (GA+AA) also exhibited risk with ESRD (p=0.045, OR=1.59). In CXCR2(+1208)C/T polymorphism, the heterozygous genotype (CT) showed significant risk for ESRD (p=0.028; OR=1.65) and combination of CT+TT demonstrated significant high risk for ESRD (p=0.036; OR=1.52). In case of CCL2I/D, the variant genotype (D/D) showed reduced risk for ESRD patients. Upon analyzing the gene-gene interaction between CXCR2 and CXCL12, the combination (CT-GA) showed 2.65 fold risk for ESRD (p=0.018).
  
  
  CONCLUSIONS
  Our results indicated that polymorphism in CXCL12G801A and CXCR2(+1208)C/T showed high risk for ESRD in North Indian population. However, CCL2I/D showed reduced risk and CCL2A2518G exhibited no association. Study with large sample size and diverse ethnicity is required to validate these observations.
authors.affiliation: Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Science, Raebareli Road, Lucknow 226014, Uttar Pradesh, India.
authors.forename: Vibha
authors.initials: V
authors.lastname: Singh
authors.forename: Praveen Kumar
authors.initials: PK
authors.lastname: Jaiswal
authors.forename: Poonam
authors.initials: P
authors.lastname: Tiwari
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kapoor
authors.forename: Rama Devi
authors.initials: RD
authors.lastname: Mittal
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000235:genetics*; D054421:Chemokine CCL21 / Q000235:genetics*; D054377:Chemokine CXCL12 / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007194:India; D007676:Kidney Failure, Chronic / Q000235:genetics*; D008297:Male; D021141:Nucleic Acid Amplification Techniques; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D023063:Receptors, Interleukin-8B / Q000235:genetics*
chemical_list: C111835:CCL2 protein, human; C515478:CCL21 protein, human; C515255:CXCL12 protein, human; D018932:Chemokine CCL2; D054421:Chemokine CCL21; D054377:Chemokine CXCL12; D023063:Receptors, Interleukin-8B
keywords: ARMS-PCR; Chemokine gene polymorphism; ESRD; Haplotype; PCR–RFLP