Vascular Endothelial Growth Factor Gene Polymorphisms Are Associated with Acute Renal Allograft Rejection

Abstract

ABSTRACT. Acute rejection is a major cause of reduced survival of renal allografts. Vascular endothelial growth factor (VEGF) is a mitogen for endothelial cells and is expressed widely by renal tissue and T cells. VEGF influences adhesion and migration of leukocytes across the endothelium. This study investigates whether genetically determined variation in VEGF expression influences the development of renal allograft rejection. VEGF promoter polymorphisms were examined by using sequence-specific primer–PCR in 173 renal transplant recipients. Acute rejection occurred in 38.7%; median time to first rejection episode was 14 d. VEGF in vitro expression was investigated in stimulated leukocytes from 30 controls. The −1154*G and −2578*C alleles were associated with higher VEGF production. VEGF −1154 GG and GA genotypes were significantly associated with acute rejection risk at 3 mo (P = 0.004, odds ration [OR] = 6.8, 95% CI = 1.8 to 25 and P = 0.035, OR = 4.1, 95% CI = 1.1 to 15, respectively). Furthermore, VEGF −2578 CC and CA genotypes were associated with increased rejection risk (P = 0.005, OR = 4.1, 95% CI = 1.5 to 11.3 and P = 0.035, OR = 2.7, 95% CI = 1.1 to 7, respectively). These polymorphisms demonstrate linkage disequilibrium (P = 0.001). These data indicate that the −1154*G and −2578*C containing genotypes, encoding higher VEGF production, are strongly associated with acute rejection and may be useful markers of rejection risk.

Influence of polymorphisms in the vascular endothelial growth factor gene on allograft rejection after kidney transplantation: a meta-analysis

“…Table S1 ( Extended data 25 ) shows the initial search using combinations of four search strings applied to four databases resulted in 1,949 citations, followed by a series of omissions that mostly involved duplications (n = 1,924), The gray literature database (Mednar) yielded no additional papers for inclusion. Thus, the final number of included articles for this meta-analysis was seven 23 , 24 , 39 – 43 .…”

“…Of the seven articles, five 23 , 24 , 39 – 41 examined more than one VEGF SNP ( Table 1 ). The number of studies VEGF1 (rs699947 and rs144854329), VEGF2 (rs1570360) and VEGF3 (rs3025039) were 10, five and three, respectively ( Table 2 ).…”

“…The number of studies VEGF1 (rs699947 and rs144854329), VEGF2 (rs1570360) and VEGF3 (rs3025039) were 10, five and three, respectively ( Table 2 ). Of the 10 VEGF1 studies, seven and three were in Indian 39 – 41 and Caucasian 23 , 24 , 43 populations, respectively. Of the five VEGF2 studies, three and two were in Indian 39 – 41 and Caucasian 23 , 24 populations, respectively.…”

“…Of the 10 VEGF1 studies, seven and three were in Indian 39 – 41 and Caucasian 23 , 24 , 43 populations, respectively. Of the five VEGF2 studies, three and two were in Indian 39 – 41 and Caucasian 23 , 24 populations, respectively. One Caucasian 42 and two Indian 40 , 41 studies comprised VEGF3.…”

“…One of the common VEGF SNPs, a cytosine (C) to adenine (A) polymorphism at position 2578 within the promoter region (-2578 C/A), was found to be associated with VEGF expression and allograft rejection. The CC genotype was associated with high VEGF production but varied in its effects on renal allograft outcomes with reduced 23 and increased 24 rejection risks across the studies. Given the varied influence of these SNPs on renal allograft function, it is opportune to statistically synthesize these study findings using meta-analysis.…”