Polymorphisms in VEGFA gene affect the antihypertensive responses to enalapril

Oliveira-Paula, Gustavo H.; Lacchini, Riccardo; Fontana, Vanessa; Silva, P. S.; Biagi, Celso; Tanus‐Santos, Jose E.

doi:10.1007/s00228-015-1872-5

Cited by 28 publications

(24 citation statements)

References 46 publications

(82 reference statements)

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“…Although PRKCA haplotypes did not significantly affect the responses to enalapril in the analysis including the total number of patients, we found that CTA haplotype is associated with worse responses to enalapril 20 mg/day. This finding is in line with previous studies showing that the effects of polymorphisms or haplotypes on the responses to antihypertensive drugs are more evident at higher doses [26,46,47]. Interestingly, the CTA haplotype includes the T and A alleles for the rs1010544 and rs16960228 polymorphisms, respectively, which are involved with worse responses to enalapril.…”

Section: Discussionsupporting

confidence: 91%

Gene–Gene Interactions Among PRKCA, NOS3 and BDKRB2 Polymorphisms Affect the Antihypertensive Effects of Enalapril

Oliveira-Paula

Luizon

Lacchini

et al. 2016

Basic Clin Pharma Tox

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Protein kinase C (PKC) signalling is critically involved in the control of blood pressure. Angiotensin-converting enzyme inhibitors (ACEi) affect PKC expression and activity, which are partially associated with the responses to ACEi. We examined whether PRKCA (protein kinase C, alpha) polymorphisms (rs887797 C>T, rs1010544 T>C and rs16960228 G>A), or haplotypes, and gene-gene interactions within the ACEi pathway affect the antihypertensive responses in 104 hypertensive patients treated with enalapril as monotherapy. Patients were classified as poor responders (PR) or good responders (GR) to enalapril if their changes in mean arterial pressure were lower or higher than the median value, respectively. Multi-factor dimensionality reduction was used to characterize interactions among PRKCA, NOS3 (nitric oxide synthase 3) and BDKRB2 (bradykinin receptor B2) polymorphisms. The TC+CC genotypes for the rs1010544 polymorphism were more frequent in GR than in PR (p = 0.037). Conversely, the GA+AA genotypes for the rs16960228 polymorphism, and the CTA haplotype, were more frequent in PR than in GR (p = 0.040 and p = 0.008, respectively). Moreover, the GG genotype for the PRKCA rs16960228 polymorphism was associated with PR or GR depending on the genotypes for the rs2070744 (NOS3) and rs1799722 (BDKRB2) polymorphisms (p = 0.012). Our results suggest that PRKCA polymorphisms and gene-gene interactions within the ACEi pathway affect the antihypertensive responses to enalapril.

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Section: Discussionsupporting

confidence: 91%

Gene–Gene Interactions Among PRKCA, NOS3 and BDKRB2 Polymorphisms Affect the Antihypertensive Effects of Enalapril

Oliveira-Paula

Luizon

Lacchini

et al. 2016

Basic Clin Pharma Tox

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“…International Journal of Hypertension 5 correlated with tumor stage and progression [29,30]. A recent study showed that polymorphisms in the VEGFA gene may affect the antihypertensive responses to enalapril [31]. In particular, A/A genotype at the rs699947 site is associated with a more intense decrease in blood pressure in response to enalapril, underlying its protective effect in hypertension, consistent with our results observed among rs699947, rs833061, and rs3025010.…”

Section: Discussionsupporting

confidence: 89%

Association between Single Nucleotide Polymorphisms in Cardiovascular Developmental Critical Genes and Hypertension: A Propensity Score Matching Analysis

Zhao

Gong

Gao

et al. 2020

International Journal of Hypertension

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Cardiovascular development critical genes are key determinants in cardiovascular diseases. We hypothesize that SNPs in these genes may play critical roles in the development of hypertension. erefore, we enrolled 516 paired hypertension patients and controls in a total of 2,742 subjects in a cross-sectional population study by the propensity score matching (PSM) method. Twentyone SNPs from 5 cardiovascular developmental related genes were detected by the improved multiplex ligase detection reaction (iMLDR) method. Conditioned logistic regression under three different genetic models, namely, additive model, dominant model, and recessive model, was performed. e odds ratio (ORs) and 95% confidence intervals (95% CIs) were used to estimate the associations of SNPs with hypertension. We found that the distribution of genotypes at rs833061, rs3025010, and rs699947 within the VEGFA gene and the distribution of alleles at rs3025010 in hypertension subjects were different from those in controls. Both rs833061 and rs3025010 were associated with hypertension in crude models, but only rs3025010 remains associated with hypertension after adjusting with confounding factors in the additive model and the dominant model. We also found that hypertension subjects with C/T and C/C genotypes at rs3025010 had lower SBP and DBP levels. In addition, rs3025010 could interact with rs6784267 within the CCM3 gene in the association. In conclusion, our findings suggest that rs3025010 may play a role in the pathogenesis of hypertension, which may be a potential target for individualized prevention and treatment of hypertension.

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“…Disruption of this gene in mice resulted in abnormal embryonic blood vessel formation, while allelic variants of this gene have been associated with microvascular complications of diabetes, atherosclerosis and the antihypertensive response to enalapril45. We previously reported a fibroblast growth factor ( FGF5 ) gene locus in association with BP10.…”

Section: Discussionmentioning

confidence: 99%

Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits

Εvangelou¹,

Warren²,

et al. 2018

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High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic, pulse pressure) to date in over one million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also reveal shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.

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Polymorphisms in VEGFA gene affect the antihypertensive responses to enalapril

Abstract: These findings suggest that polymorphisms in VEGFA gene may affect the antihypertensive responses to enalapril.

Cited by 28 publications

References 46 publications

Gene–Gene Interactions Among PRKCA, NOS3 and BDKRB2 Polymorphisms Affect the Antihypertensive Effects of Enalapril

Gene–Gene Interactions Among PRKCA, NOS3 and BDKRB2 Polymorphisms Affect the Antihypertensive Effects of Enalapril

Association between Single Nucleotide Polymorphisms in Cardiovascular Developmental Critical Genes and Hypertension: A Propensity Score Matching Analysis

Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits

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