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Vascular Endothelial Growth Factor Gene Polymorphism Is Associated With Long-term Kidney Allograft Outcomes.

ABSTRACT: Introduction: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-??Ct 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 ?2 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.

SUBMITTER: Prakash S

PROVIDER: S-EPMC5932120 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Vascular Endothelial Growth Factor Gene Polymorphism Is Associated With Long-term Kidney Allograft Outcomes.

Prakash Swayam S Patel Manas Ranjan MR Agrawal Suraksha S Jindal Rahul M RM Prasad Narayan N

Kidney international reports 20171024 2

<h4>Introduction</h4>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.<h4>Methods</h4>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 (18bpinde ...[more]

PMID: 29725635

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Project description:PurposeTo investigate the pharmacogenetic associations between the genetic risk variants of age-related macular degeneration (AMD) and long-term outcome after intravitreal anti-vascular endothelial growth factor (VEGF) treatment in Korean neovascular AMD patients.MethodsThis prospective study included 394 treatment-naïve patients (394 eyes) that underwent intravitreal anti-VEGF treatment for neovascular AMD for at least 12 months. Patients were genotyped for 17 single nucleotide polymorphisms within 13 AMD-relevant genes. Initially, patients underwent three monthly injections of intravitreal ranibizumab and were retreated as needed with ranibizumab or bevacizumab. For each candidate polymorphism, genotypic associations with treatment outcome measures at months 12 and 24, including mean change in best-corrected visual acuity (BCVA) from baseline, visual gain of ≥15 letters, mean change in central subfield macular thickness (CSMT) from baseline on spectral domain optical coherence tomography (OCT), presence of fluid on OCT, and mean number of injections, were investigated using logistic or linear regression models with adjustment for non-genetic covariates.ResultsAt month 24, BCVA improved by 4.5 ± 22.5 letters and CSMT decreased by 69.4 ± 112.6 µm from baseline. Regression analysis with Bonferroni correction showed that the TT genotype for VEGFA rs3025039 was associated with a significantly higher chance of a visual gain of ≥15 letters at month 24 than other genotypes (odds ratio, 4.57; 95% confidence interval, 1.89 - 11.1; corrected p = 0.0434). As for tomographic outcome, the minor allele homozygotes for ARMS2 rs10490924 and HTRA1 rs1100638 (GG genotype for both) were associated with a larger CSMT reduction at month 12 than other genotypes, with borderline significance after Bonferroni correction (118.6 ± 132.7 µm versus 62.7 ± 89.7 µm, corrected p = 0.0656 for rs10490924; 115.7 ± 131.7 µm versus 63.6 ± 89.8 µm, corrected p = 0.0528 for rs11200638). No polymorphism showed a significant association with the number of injections.ConclusionsIn this Korean neovascular AMD cohort, treatment outcome after anti-VEGF was found to differ by the genotypes of VEGFA rs3025039, ARMS2 rs10490924, and HTRA1 rs11200638. Given more evidence of pharmacogenetic associations with the anti-VEGF agent, individualized therapeutic approaches based on genetic background could lead to optimal treatment in neovascular AMD.

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Vascular Endothelial Growth Factor Gene Polymorphism Is Associated With Long-term Kidney Allograft Outcomes.

Publications

Vascular Endothelial Growth Factor Gene Polymorphism Is Associated With Long-term Kidney Allograft Outcomes.

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