title: Association of common variants of vascular endothelial growth factor and interleukin-18 genes with allograft survival in renal transplant recipients of North India.
abstract: Increased vascular endothelial growth factor (VEGF) production promotes enhanced endothelial permeability, enhanced leukocyte migration into the allograft, thereby leading to a clinically recognized rejection episode. Interleukin-18 (IL-18), a potent proinflammatory cytokine, may also be involved in mechanisms of kidney allograft rejection. The present study was, therefore, undertaken to investigate the association of functional polymorphisms in VEGF (2578C>A, 1154A>G) and IL-18 (607C>A, 137G>C) genes with risk of allograft rejection in renal transplant recipients of North India. Two hundred renal transplant recipients, 150 matched recipients-donors, and 200 unrelated healthy individuals were genotyped by amplification refractory mutation specific polymerase chain reaction and by polymerase chain reaction-restriction fragment length polymorphism. Variant allele VEGF 1154A>G (p = 0.56; odds ratio [OR] = 1.32) and variant allele (p = 0.004, OR = 1.54) and variant genotype (p = 0.007, OR = 3.26) of IL-18 607C>A, GC of IL-18 137G>C (p = 0.043, OR = 0.63) were significantly different in healthy individuals as compared with the patients with renal transplant. When 114 nonrejectors were compared with 36 rejectors (150 recipients) for association with allograft rejection, significant association was observed in heterozygous genotype of VEGF 2578C>A (p = 0.033), VEGF 1154A>G (p = 0.024). In IL-18 137G>C, CC genotype, C allele showed protective association with allograft rejection. Kaplan-Meier analysis indicated a higher mean time for first rejection episode in CA genotype carriers (31 months) as compared with AA (29 months) for VEGF 2578C>A (log p = 0.035). In VEGF, the haplotypes A-A and A-G (2578-1154) were associated with reduced risk and in IL-18 607A-137G, they were associated with high risk for allograft rejection. This observation suggests these polymorphisms are an ideal marker for prediction of pretransplant allograft outcome.
authors.affiliation: Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India. ramamittal@gmail.com
authors.forename: Rama Devi
authors.initials: RD
authors.lastname: Mittal
authors.forename: Priyanka
authors.initials: P
authors.lastname: Srivastava
authors.forename: Vibha
authors.initials: V
authors.lastname: Singh
authors.forename: Praveen
authors.initials: P
authors.lastname: Jaiswal
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kapoor
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D006085:Graft Survival / Q000235:genetics* / Q000276:immunology*; D006239:Haplotypes; D006801:Humans; D007194:India; D020382:Interleukin-18 / Q000235:genetics*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D055815:Young Adult
chemical_list: D005819:Genetic Markers; D020382:Interleukin-18; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A