PMID- 21323573 OWN - NLM STAT- MEDLINE DCOM- 20110711 LR - 20110506 IS - 1557-7430 (Electronic) IS - 1044-5498 (Linking) VI - 30 IP - 5 DP - 2011 May TI - Association of common variants of vascular endothelial growth factor and interleukin-18 genes with allograft survival in renal transplant recipients of North India. PG - 309-15 LID - 10.1089/dna.2010.1138 [doi] AB - 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. FAU - Mittal, Rama Devi AU - Mittal RD AD - Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India. ramamittal@gmail.com FAU - Srivastava, Priyanka AU - Srivastava P FAU - Singh, Vibha AU - Singh V FAU - Jaiswal, Praveen AU - Jaiswal P FAU - Kapoor, Rakesh AU - Kapoor R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110216 PL - United States TA - DNA Cell Biol JT - DNA and cell biology JID - 9004522 RN - 0 (Genetic Markers) RN - 0 (Interleukin-18) RN - 0 (VEGFA protein, human) RN - 0 (Vascular Endothelial Growth Factor A) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Alleles MH - Case-Control Studies MH - Child MH - Female MH - Gene Frequency MH - Genetic Markers MH - Graft Survival/*genetics/*immunology MH - Haplotypes MH - Humans MH - India MH - Interleukin-18/*genetics MH - Kidney Transplantation/*immunology MH - Male MH - Middle Aged MH - Polymorphism, Single Nucleotide MH - Risk Factors MH - Vascular Endothelial Growth Factor A/*genetics MH - Young Adult EDAT- 2011/02/18 06:00 MHDA- 2011/07/12 06:00 CRDT- 2011/02/18 06:00 PHST- 2011/02/18 06:00 [entrez] PHST- 2011/02/18 06:00 [pubmed] PHST- 2011/07/12 06:00 [medline] AID - 10.1089/dna.2010.1138 [doi] PST - ppublish SO - DNA Cell Biol. 2011 May;30(5):309-15. doi: 10.1089/dna.2010.1138. Epub 2011 Feb 16.