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. Therefore, 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. Twenty-one 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. The 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.
Highlights
Hypertension is a common chronic disease and a major risk factor for stroke, myocardial infarction, and kidney failure [1, 2]
The distribution of genotypes and alleles in Single nucleotide polymorphisms (SNPs) from the CCM3 gene was not different between hypertension and control groups, our previous study found that CCM3 gene polymorphism is associated with hypertension in an occupational population exposed to low-level arsenic, and SNPs in the CCM3 gene could interact with it, suggesting that the CCM3 gene may assist with other factors. erefore, we further examined the interaction between rs3025010 and SNPs of CCM3 genes
We found that rs3025010 within the VEGFA gene was associated with hypertension, and hypertension subjects with C/T and C/C genotypes at rs3025010 had lower SBP and DBP levels
Summary
Hypertension is a common chronic disease and a major risk factor for stroke, myocardial infarction, and kidney failure [1, 2]. Single nucleotide polymorphisms (SNPs) are DNA sequence polymorphisms caused by a single nucleotide variation at the genome level and are the most common human genetic variants [3]. Genome-wide association studies (GWASs) have enabled the discovery of common genetic variation contributing to normal and pathological traits [4, 5], suggesting that the use of SNPs as biomarkers is useful for the screening of susceptible populations and is conducive to genetic diagnosis, gene therapy for hypertension [6, 7]. It is important to note that cardiovascular development critical genes are key determinants in cardiovascular diseases [8, 9].
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