Genetic polymorphisms on VEGF (rs699947) and KDR (rs2305948and rs1870377), as well as relevant haplotypes, may serve as genetic markers that might be useful in future investigations on the pathogenesis of CHD.
Our results suggest that rs699947 (T>C) on KDR are associated with susceptibility to CHD under the dominant model before (OR=1.35, 95% CI: 1.05-1.73, P=0.019) and after (OR=1.33, 95% CI: 1.01-1.76, P=0.044), allowing for clinical characteristics (e.g., BMI, smoking, alcohol consumption, diabetes, and hypertension). rs2305948 (G>A) and rs1870377 (A>T) on VEGF were also found to be associated with risk of CHD under the recessive model after adjustment with multivariate regression analyses (OR=1.21, 95% CI: 1.02-1.43, P=0.029; OR=2.54, 95% CI: 1.13-5.75, P=0.025); OR=2.83, 95% CI: 1.47-5.46, P=0.002, respectively).
Genotype CT of rs3025039, TT of rs2305948, and AA of rs1873077 were associated with a reduced risk of CHD when smoking, alcohol intake and diabetes were considered, while homozygote GG of rs1570360 might elevate the susceptibility to CHD (all P < 0.05) for patients who were addicted to smoking or those with hypertension.
Our results suggest that rs699947 (T>C) on KDR are associated with susceptibility to CHD under the dominant model before (OR=1.35, 95% CI: 1.05-1.73, P=0.019) and after (OR=1.33, 95% CI: 1.01-1.76, P=0.044), allowing for clinical characteristics (e.g., BMI, smoking, alcohol consumption, diabetes, and hypertension). rs2305948 (G>A) and rs1870377 (A>T) on VEGF were also found to be associated with risk of CHD under the recessive model after adjustment with multivariate regression analyses (OR=1.21, 95% CI: 1.02-1.43, P=0.029; OR=2.54, 95% CI: 1.13-5.75, P=0.025); OR=2.83, 95% CI: 1.47-5.46, P=0.002, respectively).
Furthermore, three SNPs of KDR [rs7667298 (A>G), rs2305948 (C>T), rs1870377 (T>A)] were also assumed to be associated with an increased risk of aglioma in the homozygous [OR = 1.93 (95% CI 1.30-2.86, P = 0.001), OR = 2.56 (95% CI 1.28-5.11, P = 0.006), and OR = 1.52 (95% CI 1.00-2.31, P = 0.049), respectively], dominant [OR = 1.52 (95% CI 1.16-1.98, P = 0.002), OR = 1.41 (95% CI 1.05-1.87, P = 0.020), and OR = 1.48 (95% CI 1.13-1.93, P = 0.004), respectively], and allele models [OR = 1.39 (95% CI 1.15-1.67, P = 0.001), OR = 1.47 (95% CI 1.14-1.89, P = 0.002), and OR = 1.27 (95% CI 1.05-1.52, P = 0.013), respectively].
Furthermore, three SNPs of KDR [rs7667298 (A>G), rs2305948 (C>T), rs1870377 (T>A)] were also assumed to be associated with an increased risk of aglioma in the homozygous [OR = 1.93 (95% CI 1.30-2.86, P = 0.001), OR = 2.56 (95% CI 1.28-5.11, P = 0.006), and OR = 1.52 (95% CI 1.00-2.31, P = 0.049), respectively], dominant [OR = 1.52 (95% CI 1.16-1.98, P = 0.002), OR = 1.41 (95% CI 1.05-1.87, P = 0.020), and OR = 1.48 (95% CI 1.13-1.93, P = 0.004), respectively], and allele models [OR = 1.39 (95% CI 1.15-1.67, P = 0.001), OR = 1.47 (95% CI 1.14-1.89, P = 0.002), and OR = 1.27 (95% CI 1.05-1.52, P = 0.013), respectively].
A significantly higher frequency of the CC genotype of the KDR -604T>C (rs2071559) polymorphism was found in diabetic patients with MI compared to diabetic patients without CAD (27.5% vs. 21.1%, p=0.04).
The present study demonstrates that the CC genotype of the KDR -604T>C polymorphism (rs2071559) is a possible risk factor for MI in Caucasians with T2DM.
In subsequent logistic regression analyses, interactions between 2 SNPs (rs2295778 of HIF1AN, rs13337626 of TSC2) and GERD, 2 SNPs (rs2295778 of HIF1AN, rs2296188 of VEGFR1) and smoking, and 7 SNPs (rs2114039 of PDGRFA, rs2296188 of VEGFR1, rs11941492 of VEGFR1, rs17708574 of PDGFRB, rs7324547 of VEGFR1, rs17619601 of VEGFR1, and rs17625898 of VEGFR1) and BMI were significantly associated with esophageal adenocarcinoma development (all false-discovery rates ≤0.10).
This study demonstrates higher levels of VEGFR2 and frequency of AG (rs1531289</span>) genotype in AMD patient population, suggesting the role of VEGFR-2 in pathogenesis of AMD.
Three SNPs, rs2071559, rs7667298 and rs2305948, showed a statistically significant increased association with the risk of glioma (P = 0.006, 0.005, and 0.012, respectively).
Three SNPs, rs2071559, rs7667298 and rs2305948, showed a statistically significant increased association with the risk of glioma (P = 0.006, 0.005, and 0.012, respectively).
Subsequent logistic regression analysis indicated that 10 SNPs (rs2070744 of NOS3, rs720321 of BCL2, rs17757541 of BCL2, rs11775256 of TNFRSF10A, rs1035142 of CASP8, rs2236302 of MMP14, rs4740363 of ABL1, rs696217 of GHRL, rs2445762 of CYP19A1, and rs11941492 of VEGFR2/KDR) were significantly associated with early onset of EA (≤55 vs >55 years, all P < .05 after adjusting for co-variates and false discovery rate).
Carriers of variant alleles at VEGFR2 H472Q experienced greater risk of developing HT (OR(95%CI) = 2.3(1.2 - 4.6), n = 170, P = 0.0154) and HFSR (OR(95%CI) = 2.7(1.3 - 5.6), n = 170, P = 0.0136).
Our results support a genetic interaction between the VEGF-A rs3025039 and VEGFR-2 rs2071559 polymorphisms as a predictor of the risk to develop nodular goiter in subjects coming from an area with mild iodine deficiency.
Our results support a genetic interaction between the VEGF-A rs3025039 and VEGFR-2 rs2071559 polymorphisms as a predictor of the risk to develop nodular goiter in subjects coming from an area with mild iodine deficiency.
It was found that both rare homozygotes in the ANLN:rs12535394 and KDR:rs11133360 SNP pair are prognostic of favorable breast cancer survival and underpin the prominent roles of the immune response in cancer state control.
It was found that both rare homozygotes in the ANLN:rs12535394 and KDR:rs11133360 SNP pair are prognostic of favorable breast cancer survival and underpin the prominent roles of the immune response in cancer state control.
Significant G × E interactions were obtained for: rs1870377 with stress on total cholesterol (<i>p</i> = 0.035), low density lipoprotein cholesterol (<i>p</i> = 0.019), and apolipoprotein B100 (<i>p</i> = 0.004); and rs2071559 with anxiety on blood pressure (<i>p</i> = 0.006-0.045).
The rs1870377 KDR variant has shown association with RA under the codominant (<i>p</i> = 0.02, OR = 1.76, 95% CI = 1.09-2.85) and recessive models (<i>p</i> = 0.019, OR = 1.53, 95% CI = 1.07-2.20).
Our study suggested that the high expression of VEGFR-2, as well as the VEGFR-2 rs1870377 A > T genetic polymorphism, may be prognostic markers for GC.