title: Cytokine (IL-10 -1082 and -819) and chemokine receptor (CCR2 and CCR5) gene polymorphism in North Indian patients with end-stage renal disease.
abstract: End-stage renal disease (ESRD) is associated with the inflammatory state characterized by infiltrating macrophages/lymphocytes, a major source of cytokines and chemokines. This study examined the role of genetic polymorphisms in cytokine, IL-10, and chemokine receptors, CCR2 and CCR5, with susceptibility to ESRD. Polymorphisms in IL-10 (-1082 G/A, PCR-RFLP; -819 C/T, ARMS-PCR), CCR2 (Val/Ile, PCR-RFLP), and CCR5Delta32 were detected in 184 ESRD patients and 180 controls. Our results demonstrated a significant difference in genotype frequencies of IL-10 -1082G/A (p<0.001), IL-10 -819C/T (p=0.007), and CCR2Val/Ile (p=0.033) between ESRD patients and controls. However, only low-producing genotype AA of IL-10 -1082G/A showed significantly threefold higher risk for all ESRD patients (odds ratio [OR]=3.164, 95%CI=1.74-5.72) as well as patients with only inflammatory causes of renal diseases (OR=2.979, 95%CI=1.61-5.52). No risk was seen in variant genotype of other genes. The genotypic frequencies of CCR5Delta32 were comparable in patients and controls (p=0.203). In haplotype analysis, A-T haplotype (low producer) of IL-10 showed 1.7-fold risk (p>0.05). No risk was seen for CCR2 and CCR5 haplotypes. The AA genotype of IL-10 -1082G/A polymorphism was associated with increased susceptibility to ESRD. This study implies the basis for defined antiinflammatory approaches to impede renal disease progression.
authors.affiliation: Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Parmeet Kaur
authors.initials: PK
authors.lastname: Manchanda
authors.forename: Ranjana
authors.initials: R
authors.lastname: Singh
authors.forename: Rama Devi
authors.initials: RD
authors.lastname: Mittal
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007194:India; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology; D007676:Kidney Failure, Chronic / Q000235:genetics* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D054390:Receptors, CCR2 / Q000235:genetics* / Q000276:immunology; D019713:Receptors, CCR5 / Q000235:genetics* / Q000276:immunology; D055815:Young Adult
chemical_list: C515334:CCR2 protein, human; C508609:IL10 protein, human; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D016753:Interleukin-10