- Association of Donor's Vascular Endothelial Growth Factor gene polymorphism with Allograft Survival in Renal Transplant Recipients
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Narayan Prasad, Vinita Agarwal, Manas Ranjan Patel
2021 ; 2021(1):
- 논문분류 :
- 춘계학술대회 초록집
Objective: Genotyping of VEGF SNPs among 320 recipients and 160 donors were done through PCR- RFLP technique; the recipient group was divided into non-rejecters (160) and rejecters (160) and analyzed further. VEGF serum levels were checked through ELISA. Intragraft expression of VEGF mRNA and protein was analyzed by RT-PCR and IHC technique Methods: 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 and serum VEGF level was significantly higher in allograft recipients compared to healthy donor, which was further higher in rejecters compared to non-rejecters. On IHC percentage of VEGF staining in glomerular capillaries and cortical peritubular capillaries was higher in rejection as compared to non-rejection. Results: Mutant genotypes of VEGF +936 C>T, -1190G>A, -2549 18bp Insertion/Deletion and -1455T>C SNPs was associated with increased risk for renal allograft rejection. Conclusions: Objective: Vascular Endothelial Growth Factor (VEGF) is a pro-angiogenic factor, requires for maintenance of the physiological function of endothelium cells. The impact of donor-associated VEGF polymorphism is not studied in renal allograft recipients. Methods: Genotyping of VEGF SNPs among 320 recipients and 160 donors were done through PCR- RFLP technique; the recipient group was divided into non-rejecters (160) and rejecters (160) and analyzed further. VEGF serum levels were checked through ELISA. Intragraft expression of VEGF mRNA and protein was analyzed by RT-PCR and IHC technique 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 and serum VEGF level was significantly higher in allograft recipients compared to healthy donor, which was further higher in rejecters compared to non-rejecters. On IHC percentage of VEGF staining in glomerular capillaries and cortical peritubular capillaries was higher in rejection as compared to non-rejection. Conclusions: Mutant genotypes of VEGF +936 C>T, -1190G>A, -2549 18bp Insertion/Deletion and -1455T>C SNPs was associated with increased risk for renal allograft rejection.