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Abstract: PO2177

Association of Vascular Endothelial Growth Factor Gene Polymorphism with Allograft Survival in Renal Transplant Recipients

Session Information

Category: Transplantation

  • 1902 Transplantation: Clinical

Authors

  • Prasad, Narayan, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
  • Patel, Manas Ranjan, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
  • Agrawal, Vinita, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Background

Endothelial cell dysfunction is a primary cause for late allograft loss in renal transplantation recipients. Vascular Endothelial Growth Factor (VEGF) is a pro-angiogenic factor that has an important role in the development and maintenance of physiological function of endothelium cell thus may determines the allograft function.

Methods

We did genotyping of VEGF SNPs among 320 renal allograft recipients(non-rejecters (160) and rejecters (160)) and 160 donors by PCR- RFLP technique. Intragraft VEGF mRNA and protein expression were analyzed by RT-PCR and immunohistochemistry. Serum VEGF level were analyzed by ELISA.

Results

On comparison between donors and recipients genotypes of VEGF +936 C>T [CT (OR=7.16; 95% CI=4.33- 11.84; P=0.00) and TT (OR=49.30; 95% CI=11.84-205.29; P=0.00)], -1154 G>A [AG (OR=2.22; 95% CI=1.40-3.50; P=0.00)], -1190G>A [GG (OR=2.21; 95% CI=1.22-4.01; P=0.00)], -634C>G [GG (OR=2.34; 95% CI=1.34-4.10; P=0.00)], -2549 18bp Insertion/Deletion [ID (OR=1.58; 95% CI=1.01- 2.46; P=0.04) were significantly associated with risk of rejection. On comparing mutant genotypes between non-rejecters and rejecters we found that genotypic frequencies of +936 C>T [TT (OR=2.43; 95% CI=1.33-4.44; P=0.004)], -1154 G>A [GG (OR=1.94; 95% CI=1.03-3.67; P=0.04)], -1190G>A [GA (OR=1.83; 95% CI=1.07-3.13; P=0.02)], -2549 18bp Insertion/Deletion [ID (OR=2.35; 95% CI=1.38- 3.99; P=0.002) and -1455T>C [TT (OR=3.13; 95% CI=1.07-9.10; P=0.03)] shown risk of allograft rejection whereas mutant genotypes of -2578 C>A [ CA (OR=0.45; 95% CI=0.26-0.79; P=0.005) and CC (OR=0.23; 95% CI=0.11-0.46; P=0.000)] and +405 C>G [GG (OR=0.43; 95% CI=0.20-0.91; P=0.02)] have shown protective association with rejection. The VEGF mRNA expression was also significantly higher in rejecters compared to non-rejecters which both were higher compared to healthy donor. Mean serum VEGF levels was higher in rejecters compared to non-rejecters, which both were higher than those of donors. On IHC percentage of VEGF staining in glomerular capillaries and cortical peritubular capillaries was higher in rejecter as compared to non-rejecter.

Conclusion

The present study signifies genetic associations of all the mutant genotypes of VEGF +936 C>T, -1190G>A, -2549 18bp Insertion/Deletion, and -1455T>C SNPs to be at increased risk for renal allograft rejection.

Funding

  • Government Support – Non-U.S.