Vascular Endothelial Growth Factor Gene Polymorphism Is Associated With Long-term Kidney Allograft Outcomes
Vascular endothelial growth factor (VEGF) regulates vasculogenesis in physiological and pathological states. We evaluated the role of VEGF single-nucleotide polymorphisms (SNPs) −1154 G/A, −2578 C/A, +936 C/T, and −2549 Ins/Del in chronic allograft nephropathy. Methods: Blood samples were collected...
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| Format: | Article |
| Language: | English |
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Elsevier
2018-03-01
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| Series: | Kidney International Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468024917304266 |
| _version_ | 1828826926932819968 |
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| author | Swayam Prakash Manas Ranjan Patel Suraksha Agrawal Rahul M. Jindal Narayan Prasad |
| author_facet | Swayam Prakash Manas Ranjan Patel Suraksha Agrawal Rahul M. Jindal Narayan Prasad |
| author_sort | Swayam Prakash |
| collection | DOAJ |
| description | Vascular endothelial growth factor (VEGF) regulates vasculogenesis in physiological and pathological states. We evaluated the role of VEGF single-nucleotide polymorphisms (SNPs) −1154 G/A, −2578 C/A, +936 C/T, and −2549 Ins/Del in chronic allograft nephropathy.
Methods: Blood samples were collected before renal transplantation, and DNA was extracted. Genotyping of VEGF SNPs −1154 G/A (rs1570360), −2578 C/A (rs699947), +936 C/T (rs112005313), and −2549 Ins/Del (18bpindel) polymorphisms were carried out. Relative quantification of VEGF-A mRNA expression for 4 VEGF SNPs were quantified by the 2−ΔΔCt algorithm. Kidney allografts were categorized into graft loss (n = 98) and normally functioning (n = 174) groups. Genotype frequencies were calculated using additive, dominant, and recessive models. Hardy−Weinberg Equilibrium was assessed between outcome groups by standard procedure using χ2 analysis. The cumulative allograft survival was estimated by Kaplan−Meier analysis and compared among VEGF genotypes by the log-rank test. Study limitations were the lack of VEGF serum levels, donor-specific antigens, and protocol biopsies.
Results: There was an association of AA (hazard ratio = 2.42, P = 0.0001) and CA (hazard ratio = 1.83, P = 0.009) genotypes of −2578 C/A SNP with graft loss. After adjustment for transplant-related covariates, associations of VEGF SNPs −2578 C/A and −2549 Ins/Del with graft failure were found to be significant. There was prolonged graft survival for cases with the CC genotype of VEGF −2578 C/A SNP. The carrier −2578*CC, −1154*GG, and +936*CC genotypes were shown to have a strongly protective association. There was no association with posttransplantation lymphomas.
Conclusion: Recipients of kidney allografts possessing low-producing VEGF genotypes are associated with less prolonged graft survival. |
| first_indexed | 2024-12-12T14:49:35Z |
| format | Article |
| id | doaj.art-5b34a94c03824f63a49bdc8d2ee85788 |
| institution | Directory Open Access Journal |
| issn | 2468-0249 |
| language | English |
| last_indexed | 2024-12-12T14:49:35Z |
| publishDate | 2018-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Kidney International Reports |
| spelling | doaj.art-5b34a94c03824f63a49bdc8d2ee857882022-12-22T00:21:02ZengElsevierKidney International Reports2468-02492018-03-013232132710.1016/j.ekir.2017.10.008Vascular Endothelial Growth Factor Gene Polymorphism Is Associated With Long-term Kidney Allograft OutcomesSwayam Prakash0Manas Ranjan Patel1Suraksha Agrawal2Rahul M. Jindal3Narayan Prasad4Department of Nephrology and Renal Transplantation, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, IndiaDepartment of Nephrology and Renal Transplantation, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, IndiaDepartment of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, IndiaUniformed Services University–Walter Reed Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USADepartment of Nephrology and Renal Transplantation, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, IndiaVascular endothelial growth factor (VEGF) regulates vasculogenesis in physiological and pathological states. We evaluated the role of VEGF single-nucleotide polymorphisms (SNPs) −1154 G/A, −2578 C/A, +936 C/T, and −2549 Ins/Del in chronic allograft nephropathy. Methods: Blood samples were collected before renal transplantation, and DNA was extracted. Genotyping of VEGF SNPs −1154 G/A (rs1570360), −2578 C/A (rs699947), +936 C/T (rs112005313), and −2549 Ins/Del (18bpindel) polymorphisms were carried out. Relative quantification of VEGF-A mRNA expression for 4 VEGF SNPs were quantified by the 2−ΔΔCt algorithm. Kidney allografts were categorized into graft loss (n = 98) and normally functioning (n = 174) groups. Genotype frequencies were calculated using additive, dominant, and recessive models. Hardy−Weinberg Equilibrium was assessed between outcome groups by standard procedure using χ2 analysis. The cumulative allograft survival was estimated by Kaplan−Meier analysis and compared among VEGF genotypes by the log-rank test. Study limitations were the lack of VEGF serum levels, donor-specific antigens, and protocol biopsies. Results: There was an association of AA (hazard ratio = 2.42, P = 0.0001) and CA (hazard ratio = 1.83, P = 0.009) genotypes of −2578 C/A SNP with graft loss. After adjustment for transplant-related covariates, associations of VEGF SNPs −2578 C/A and −2549 Ins/Del with graft failure were found to be significant. There was prolonged graft survival for cases with the CC genotype of VEGF −2578 C/A SNP. The carrier −2578*CC, −1154*GG, and +936*CC genotypes were shown to have a strongly protective association. There was no association with posttransplantation lymphomas. Conclusion: Recipients of kidney allografts possessing low-producing VEGF genotypes are associated with less prolonged graft survival.http://www.sciencedirect.com/science/article/pii/S2468024917304266chronic allograft dysfunctionsingle-nucleotide polymorphismvascular endothelial growth factorVEGF −2578 C/A |
| spellingShingle | Swayam Prakash Manas Ranjan Patel Suraksha Agrawal Rahul M. Jindal Narayan Prasad Vascular Endothelial Growth Factor Gene Polymorphism Is Associated With Long-term Kidney Allograft Outcomes Kidney International Reports chronic allograft dysfunction single-nucleotide polymorphism vascular endothelial growth factor VEGF −2578 C/A |
| title | Vascular Endothelial Growth Factor Gene Polymorphism Is Associated With Long-term Kidney Allograft Outcomes |
| title_full | Vascular Endothelial Growth Factor Gene Polymorphism Is Associated With Long-term Kidney Allograft Outcomes |
| title_fullStr | Vascular Endothelial Growth Factor Gene Polymorphism Is Associated With Long-term Kidney Allograft Outcomes |
| title_full_unstemmed | Vascular Endothelial Growth Factor Gene Polymorphism Is Associated With Long-term Kidney Allograft Outcomes |
| title_short | Vascular Endothelial Growth Factor Gene Polymorphism Is Associated With Long-term Kidney Allograft Outcomes |
| title_sort | vascular endothelial growth factor gene polymorphism is associated with long term kidney allograft outcomes |
| topic | chronic allograft dysfunction single-nucleotide polymorphism vascular endothelial growth factor VEGF −2578 C/A |
| url | http://www.sciencedirect.com/science/article/pii/S2468024917304266 |
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