Cytokine (IL-10 -1082 and -819) and chemokine receptor (CCR2 and CCR5) gene polymorphism in North Indian patients with end-stage renal disease.
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.
Manchanda
Parmeet Kaur
PK
Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
Singh
Ranjana
R
Mittal
Rama Devi
RD
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
C515334:CCR2 protein, human; C508609:IL10 protein, human; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D016753:Interleukin-10