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

Abstract

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.

Association of AGTR1 (rs5186), VDR (rs2228570) genes polymorphism with blood pressure elevation in patients with essential arterial hypertension

“…Mutations in the genes encoding RAAS are being actively studied worldwide, but their role in the pathogenesis of EAH is not entirely elucidated [ 1 , 4 , 5 , 8 , 9 , 11 ]. Numerous studies have shown the association of AGTR1 gene 1166A>C (rs5186) polymorphism with arterial hypertension, vasoconstriction, and sodium retention in the body [ 9 , 10 ].…”

“…As a polygenic disease, arterial hypertension occurs due to the environmental and genetic predictors interactions in linkage with epigenomic structures. Most of the genetic variations associated with EAH that were collected in Genome-Wide Association Studies (GWASs) [ 4 – 5 ], where SNPs which play the role of possible biomarkers for hypertension screening [ 5 – 8 ]. The renin-angiotensin-aldosterone system (RAAS) is a complex multilevel mechanism regulating vascular tone, metabolic homeostasis, water, and electrolyte balance.…”

VEGF-A related SNPs: a cardiovascular context

“…High VEGF-A levels are associated with various CVD risk factors including smoking, hypercholesterolemia, diabetes, hypertension, and hyperglycemia ( 36 ). Additionally, increased VEGF-A activity has been associated with inflammation, increased blood pressure and an increase in the formation of atherosclerotic lesions, leading to CHD ( 20 , 69 – 71 ). The impact of angiogenic molecules on atherosclerosis has been reviewed elsewhere ( 39 ).…”

“…An additional variant that has shown association to the cardiovascular system is rs3025010 located in intron 5 ( Figure 2B ). In a Chinese cohort diagnosed with hypertension the C allele of this variant was observed to be associated with lower systolic and diastolic blood pressure measurements ( 20 ). Furthermore, in a Chinese case-control study, it was observed that the CC genotype of rs3025010 reduced risk of brain arteriovenous malformation ( 91 ).…”

“…Considering this genetic complexity, numerous studies have focused on identifying associations between genetic variants and common cardiovascular disease traits (15,(18)(19)(20)(21). This has been supported with the establishment of genome wide association studies (GWAS), which employ technologies that detect many gene variants simultaneously (22).…”