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Angiotensinógeno , Hipertensión , ARN Interferente Pequeño , Animales , Humanos , Angiotensinógeno/genética , Angiotensinógeno/metabolismo , Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/genética , Hipertensión/genética , Hipertensión/fisiopatología , Hipertensión/tratamiento farmacológico , Hipertensión/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/uso terapéuticoRESUMEN
OBJECTIVE: Apolipoprotein E (APOE) gene polymorphisms were associated with coronary atherosclerosis and hypertension. However, the relationship between APOE polymorphisms and coronary atherosclerosis susceptibility in hypertensive patients is unclear. The aim of this study was to assess the relationship. METHODS: A total of 1713 patients with hypertension who were admitted to Meizhou People's Hospital from November 2019 to August 2023 were retrospectively analyzed, including 848 patients with coronary atherosclerosis and 865 patients without coronary atherosclerosis. The rs429358 and rs7412 polymorphisms of APOE were genotyped, and relationship between APOE polymorphisms and the risk of coronary atherosclerosis in hypertensive patients were analyzed. RESULTS: There were 10 (0.6%), 193 (11.3%), 30 (1.8%), 1234 (72.0%), 233 (13.6%), and 13 (0.8%) individuals with APOE É2/É2, É2/É3, É2/É4, É3/É3, É3/É4, and É4/É4 genotype, respectively. The frequency of APOE É3/É4 was higher (16.4% vs. 10.9%, p = 0.001) in the patients with coronary atherosclerosis than controls. Logistic analysis showed that body mass index (BMI) ≥ 24.0 kg/m2 (24.0 kg/m2 vs. 18.5-23.9 kg/m2, odds ratio (OR): 1.361, 95% confidence interval (CI): 1.112-1.666, p = 0.003), advanced age (≥ 65/<65, OR:1.303, 95% CI: 1.060-1.602, p = 0.012), history of smoking (OR: 1.830, 95% CI: 1.379-2.428, p < 0.001), diabetes mellitus (OR: 1.380, 95% CI: 1.119-1.702, p = 0.003), hyperlipidemia (OR: 1.773, 95% CI: 1.392-2.258, p < 0.001), and APOE É3/É4 genotype (É3/É4 vs. É3/É3, OR: 1.514, 95% CI: 1.133-2.024, p = 0.005) were associated with coronary atherosclerosis in hypertensive patients. CONCLUSIONS: Overweight (BMI ≥ 24.0 kg/m2), advanced age, history of smoking, diabetes mellitus, and APOE É3/É4 genotype were independent risk factors for coronary atherosclerosis in hypertensive patients.
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Apolipoproteína E3 , Apolipoproteína E4 , Enfermedad de la Arteria Coronaria , Predisposición Genética a la Enfermedad , Hipertensión , Humanos , Masculino , Femenino , Enfermedad de la Arteria Coronaria/genética , Persona de Mediana Edad , Hipertensión/genética , Hipertensión/epidemiología , Hipertensión/diagnóstico , Estudios Retrospectivos , Medición de Riesgo , Anciano , Factores de Riesgo , Apolipoproteína E3/genética , Apolipoproteína E4/genética , China/epidemiología , Fenotipo , Polimorfismo de Nucleótido Simple , Estudios de Asociación Genética , Apolipoproteínas EAsunto(s)
Retinopatía Diabética , Hipertensión , Presión Intraocular , Análisis de la Aleatorización Mendeliana , Humanos , Retinopatía Diabética/genética , Retinopatía Diabética/epidemiología , Retinopatía Diabética/etiología , Hipertensión/genética , Hipertensión/epidemiología , Presión Intraocular/fisiologíaRESUMEN
Interleukin-6 (IL-6) plays a crucial role in the pathogenesis of cardiovascular disease (CVD), and IL-6 receptor (IL-6R) blockade has emerged as a promising therapeutic option. However, their specific therapeutic effects in different types of CVDs remain unclear. This study aimed to assess the efficacy of IL-6R blockade in the management of various CVDs, including hypertension (HTN), coronary heart disease (CHD), myocardial infarction (MI), atrial fibrillation (AF), and heart failure (HF). The Mendelian randomization (MR) approach was utilized to investigate the therapeutic impact of IL-6R blockade on HTN, CHD, MI, AF, and HF based on the genome-wide association study (GWAS) summary statistics. MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis were used for sensitivity analysis to verify the reliability of the MR results. The Bonferroni method was used to correct for bias caused by multiple comparisons. Inverse variance weighted (IVW) results demonstrated that IL-6R blockade significantly influenced CHD (odds ratio (OR) = 0.757, 95% confidence interval (CI): 0.690 - 0.832, P = 5.804 × 10-9) and MI (OR = 0.840, 95% CI: 0.744 - 0.949, P = 0.005). However, IL-6R blockade had no significant effect on HTN (OR = 1.015, 95% CI: 0.950 - 1.084, P = 0.663), AF (OR = 0.905, 95% CI: 0.800 - 1.025, P = 0.116) and HF (OR = 1.012, 95% CI: 0.921 - 1.113, P = 0.805). Genetically predicted IL-6R blockade was associated with a protective effect on CHD and MI, but not HTN, AF and HF. This study's findings offer valuable insights for tailoring IL-6R blockade treatment for different types of CVD, and serve as a reference for future research.
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Enfermedades Cardiovasculares , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Receptores de Interleucina-6 , Humanos , Receptores de Interleucina-6/antagonistas & inhibidores , Receptores de Interleucina-6/genética , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/tratamiento farmacológico , Polimorfismo de Nucleótido Simple , Interleucina-6/antagonistas & inhibidores , Interleucina-6/genética , Hipertensión/tratamiento farmacológico , Hipertensión/genética , Infarto del Miocardio/genética , Infarto del Miocardio/tratamiento farmacológicoRESUMEN
BACKGROUND: The lipid-lowering effects of Omega-3 fatty acids have been widely reported, yet their impact on ischemic stroke remains controversial. Reports on the protective effects of unsaturated fatty acids, such as Omega-6 and Omega-7, as well as saturated fatty acids in cardiovascular diseases, including hypertension and ischemic stroke, are less frequent. OBJECTIVES: This study aims to identify fatty acids associated with blood pressure and ischemic stroke through Mendelian randomization. Besides, it seeks to determine whether specific fatty acids can prevent ischemic stroke by managing blood pressure and revealing the specific mechanisms of this action. METHODS: This research involved downloading relevant data from websites and extracting SNPs that met the standard criteria as instrumental variables. Simultaneously, the 'MR-PRESSO' package and 'Mendelian Randomization' package were used to eliminate confounding SNPs that could bias the study results. Then, inverse variance weighting and the weighted median were employed as primary analysis methods, accompanied by sensitivity analysis to assess the validity of the causal relationships. Initially, multivariable Mendelian randomization was used to identify fatty acids linked to blood pressure and the incidence of ischemic stroke. The causal link between certain fatty acids and the initiation of ischemic stroke was then investigated using bidirectional and mediator Mendelian randomization techniques. Stepwise Regression and the Product of Coefficients Method in mediator Mendelian randomization were utilized to ascertain whether specific fatty acids reduce ischemic stroke risk by lowering blood pressure. RESULTS: Multivariable Mendelian randomization analysis indicated a potential inverse correlation between Omega-3 intake and both blood pressure and ischemic stroke. Consequently, Omega-3 was selected as the exposure, with blood pressure and ischemic stroke-related data as outcomes, for further bidirectional and mediation Mendelian Randomization analyses. Bidirectional Mendelian Randomization revealed that Omega-3 significantly influences DBP (P = 1.01e-04) and IS (P = 0.016). It also showed that DBP and SBP significantly affect LAS, SVS, CES, IS, and LS. Mediator Mendelian Randomization identified five established mediating pathways: Omega-3-Diastolic blood pressure-Small vessel stroke, Omega-3-Diastolic blood pressure-Cardioembolic stroke, Omega-3-Diastolic blood pressure-Lacunar stroke, Omega-3-Diastolic blood pressure-Large artery atherosclerosis stroke, and Omega-3-Diastolic blood pressure-Ischemic stroke. Of these, four pathways are complete mediation, and one pathway is partial mediation. CONCLUSIONS: The findings suggest that Omega-3 may indirectly reduce the incidence of ischemic stroke by lowering blood pressure. Thus, blood pressure modulation might be one of the mechanisms through which Omega-3 prevents ischemic stroke. In summary, incorporating an increased intake of Omega-3 in the diet can serve as one of the dietary intervention strategies for patients with hypertension. Additionally, it can act as an adjunctive therapy for the prevention of ischemic strokes and their complications.
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Presión Sanguínea , Ácidos Grasos Omega-3 , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Accidente Cerebrovascular , Ácidos Grasos Omega-3/uso terapéutico , Humanos , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/genética , Hipertensión/genética , Factores de RiesgoRESUMEN
OBJECTIVE: Aim: To understand how vitamin D receptor gene polymorphism (VDR rs2228570) affects blood pressure in Iraqi patients with essential hypertension in Al Diwaniya province. PATIENTS AND METHODS: Materials and Methods: This is a single-center observational cross-sectional descriptive study of 90 patients with essential hypertension. Using the PCRTETRA ARM technique, blood samples were genotyped and examined for the polymorphisms of FOKI (rs2228570) gene. RESULTS: Results: The most frequent allele was A (121, 67%) while the most frequent genotype was AG (55, 61%). There was no statistical difference between the actual and expected frequency distribution, according to Hardy-Weinberg equilibrium. The effect of VDR polymorphism rs 2228570 on blood pressure indicates (the mean systolic blood pressure in AA, AG, and GG carrier patients was 149, 150 and 166 respectively, P=0.29. On the other hand, the mean diastolic blood pressure in AA, AG, and GG carrier patients was 89, 89, and 94 respectively P=0.6) there was no statistically significant effect on systolic and diastolic blood pressure. CONCLUSION: Conclusions: there is no statistically significant effect of VDR rs2228570 on SBP and DBP (p = 0.6), vitamin D receptor gene polymorphism rs2228570 was related to vitamin D level.
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Hipertensión Esencial , Receptores de Calcitriol , Humanos , Receptores de Calcitriol/genética , Irak , Masculino , Femenino , Estudios Transversales , Hipertensión Esencial/genética , Persona de Mediana Edad , Hipertensión/genética , Adulto , Polimorfismo Genético , Predisposición Genética a la Enfermedad , Presión Sanguínea/genética , Polimorfismo de Nucleótido Simple , Genotipo , AncianoRESUMEN
OBJECTIVE: Aim: To investigate allele frequencies of rs1799983 polymorphism eNOS genes and to determine association between rs1799983 polymorphism of eNOS gene and essential hypertension in Iraqi hypertensive patients. PATIENTS AND METHODS: Materials and Methods: This is an observational cross sectional descriptive single center study. ninety hypertensive patients were recruited by specialist cardiologist and conducted at AL-Diwaniyah teaching hospital and department of pharmacology and therapeutics, college of medicine, university of Al-Qadisiyah, Iraq. DNA samples were genotyped by PCR-tetra-arm method. NO level was measured by using ELISA kit. RESULTS: Results: Regarding rs1799983 the most frequent allele was G (73%) and the most frequent genotype was GG (55%). Our results indicate lack of substantial link between genotype frequencies of rs1799983 polymorphism and NO level (p=0.88) and thereby there is no statistically significant effect on SBP and DBP (p = 0.051). CONCLUSION: Conclusions: our study demonstrated lack of significant association between this polymorphism and essential hypertension in Iraqi hypertensive patients.
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Hipertensión Esencial , Óxido Nítrico Sintasa de Tipo III , Humanos , Irak , Óxido Nítrico Sintasa de Tipo III/genética , Masculino , Femenino , Estudios Transversales , Hipertensión Esencial/genética , Persona de Mediana Edad , Hipertensión/genética , Adulto , Polimorfismo de Nucleótido Simple , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , GenotipoRESUMEN
OBJECTIVE: Aim: To investigate lipid profile parameters depending the polymorphism of the A1166C I type gene receptor of the angiotensin II as a predictor of arterial hypertension. PATIENTS AND METHODS: Materials and Methods: The study involved 86 patients with arterial hypertension. The control group consisted of 30 practically healthy individuals. Indicators of lipid metabolism in the blood serum of patients were determined using "Lachema" kits on an analyzer. The the polymorphism of the A1166C I type gene receptor of the angiotensin II was studied by polymerase chain reaction with electrophoretic detection of the results. RESULTS: Results: Higher levels of total cholesterol were found in patients with CC genotype compared to AA genotype carriers ((8.94±0.09) vs (5.18±0.02) mmol/L). The level of low-density lipoprotein in CC-genotype carriers was (7.43±0.03) versus (3.66±0.02) mmol/L in A-allele homozygotes. Triglycerides and very low density lipoproteins were also significantly higher in CC genotype carriers compared to patients with AA genotype. The level of high-density lipoprotein was lower in homozygotes with C-allele than in patients with the AA genotype, and was (0.59±0.12) versus (0.99±0.03) mmol/L. CONCLUSION: Conclusions: The presence in the CC genotype the I type gene receptor of the angiotensin II type is a predictor of dyslipidemia. In patients with arterial hypertension, the presence in the C-allele of the I type gene of the angiotensin II type contributes to a significant increase in serum adipokines and a decrease in ghrelin levels.
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Hipertensión , Polimorfismo Genético , Receptor de Angiotensina Tipo 1 , Humanos , Hipertensión/genética , Hipertensión/sangre , Masculino , Femenino , Receptor de Angiotensina Tipo 1/genética , Persona de Mediana Edad , Lípidos/sangre , Adulto , GenotipoRESUMEN
The study investigated the causal relationships between spermidine levels and CVD risk factors using a bi-directional MR approach. Employing genetic variants from extensive GWAS datasets as IVs, the study aimed to determine whether spermidine levels can influence CVD risk factors such as blood pressure, blood glucose, and lipid profiles, and vice versa. The findings suggest a protective role of elevated spermidine levels against hypertension, elevated blood glucose, and lipid profiles (LDL-C and HDL-C). Specifically, increased spermidine levels were significantly associated with lower risk of hypertension (IVW beta = -0.0013453913, p = 0.01597648) and suppression risk of elevated blood glucose (IVW beta = -0.08061330, p = 0.02450205). Additionally, there was a notable association with lipid modulation, showing a decrease in LDL-C (IVW beta = -0.01849161, p = 0.01086728) and an increase in HDL-C (IVW beta = 0.0044608332, P = 0.01760051). Conversely, the influence of CVD risk factors on spermidine levels was minimal, with the exception that elevated blood glucose levels resulted in reduced spermidine levels. (IVW beta = -0.06714391, P = 0.01096123). These results underline the potential of spermidine as a modifiable dietary target for the prevention and management of cardiovascular diseases. Further investigations are warranted to explore the underlying biological mechanisms and the applicability of these findings in broader and diverse populations.
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Enfermedades Cardiovasculares , Factores de Riesgo de Enfermedad Cardiaca , Análisis de la Aleatorización Mendeliana , Espermidina , Espermidina/sangre , Humanos , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/genética , Glucemia/metabolismo , Hipertensión/genética , Hipertensión/sangre , Estudio de Asociación del Genoma Completo , Presión Sanguínea , LDL-Colesterol/sangre , Causalidad , Factores de Riesgo , HDL-Colesterol/sangreRESUMEN
Two researchers independently assessed studies published up to February 5, 2023, across PubMed, Web of Science, Embase, and Cochrane Library, to investigate the associations of sleep traits with cardiometabolic risk factors, as well as with cardiovascular diseases. Fourteen systematic reviews consisting of 23 meta-analyses, and 11 Mendelian randomization (MR) studies were included in this study. Short sleep duration was associated with a higher risk of obesity, type 2 diabetes (T2D), hypertension, stroke, and coronary heart disease (CHD) in observational studies, while a causal role was only demonstrated in obesity, hypertension, and CHD by MR. Similarly, long sleep duration showed connections with a higher risk of obesity, T2D, hypertension, stroke, and CHD in observational studies, none was supported by MR analysis. Both observational and MR studies indicated heightened risks of hypertension, stroke, and CHD in relation to insomnia. Napping was linked to elevated risks of T2D and CHD in observational studies, with MR analysis confirming a causal role in T2D. Additionally, snoring was correlated with increased risks of stroke and CHD in both observational and MR studies. This work consolidates existing evidence on a causal relationship between sleep characteristics and cardiometabolic risk factors, as well as cardiovascular diseases.
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Factores de Riesgo Cardiometabólico , Enfermedades Cardiovasculares , Análisis de la Aleatorización Mendeliana , Sueño , Humanos , Sueño/fisiología , Diabetes Mellitus Tipo 2/genética , Estudios Observacionales como Asunto , Obesidad/complicaciones , Obesidad/genética , Hipertensión/genética , Accidente Cerebrovascular , Factores de RiesgoRESUMEN
Although Akkermansia muciniphila (Am) plays a beneficial role as a probiotic in the treatment of metabolic syndrome, the mechanisms remain elusive. We tested the hypothesis that Am extracellular vesicles (AmEVs) protect against hypertension through modulation of gene expression in the kidneys of spontaneously hypertensive rats (SHRs). Extracellular vesicles purified from anaerobically cultured Am (1.0 × 108 or 1.0 × 109 particles/kg) or vehicles were injected into the tail veins of Wistar-Kyoto rats (WKYs) and SHRs weekly for 4 weeks. Renal cortical tissues isolated from both rat strains were analyzed by trichrome stain and RT-qPCR. AmEVs protect against the development of hypertension in SHRs without a serious adverse reaction. AmEVs increased the expression of vasocontracting Agt and At1ar as well as vasodilating At2r, Mas1 and Nos2 in the kidneys of both strains. These results indicate that AmEVs have a protective effect against hypertension without a serious adverse reaction. Therefore, it is foreseen that AmEVs may be utilized as a novel therapeutic for the treatment of hypertension.
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Akkermansia , Vesículas Extracelulares , Hipertensión , Riñón , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Animales , Vesículas Extracelulares/metabolismo , Ratas , Riñón/metabolismo , Hipertensión/metabolismo , Hipertensión/genética , Masculino , Administración Intravenosa , Verrucomicrobia/genética , Regulación de la Expresión Génica , Probióticos/administración & dosificaciónAsunto(s)
Hipertensión , Estilo de Vida , Humanos , Hipertensión/genética , Hipertensión/epidemiología , Asia/epidemiologíaRESUMEN
Activation of the renin-angiotensin-aldosterone system (RAAS) plays an important pathophysiological role in hypertension. Increased mRNA levels of the angiotensinogen angiotensin-converting enzyme, angiotensin type 1 receptor gene, Agtr1a, and the aldosterone synthase gene, CYP11B2, have been reported in the heart, blood vessels, and kidneys in salt-sensitive hypertension. However, the mechanism of gene regulation in each component of the RAAS in cardiovascular and renal tissues is unclear. Epigenetic mechanisms, which are important for regulating gene expression, include DNA methylation, histone post-translational modifications, and microRNA (miRNA) regulation. A close association exists between low DNA methylation at CEBP-binding sites and increased AGT expression in visceral adipose tissue and the heart of salt-sensitive hypertensive rats. Several miRNAs influence AGT expression and are associated with cardiovascular diseases. Expression of both ACE and ACE2 genes is regulated by DNA methylation, histone modifications, and miRNAs. Expression of both angiotensinogen and CYP11B2 is reversibly regulated by epigenetic modifications and is related to salt-sensitive hypertension. The mineralocorticoid receptor (MR) exists in cardiovascular and renal tissues, in which many miRNAs influence expression and contribute to the pathogenesis of hypertension. Expression of the 11beta-hydroxysteroid dehydrogenase type 2 (HSD11B2) gene is also regulated by methylation and miRNAs. Epigenetic regulation of renal and vascular HSD11B2 is an important pathogenetic mechanism for salt-sensitive hypertension.
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Metilación de ADN , Epigénesis Genética , Hipertensión , Sistema Renina-Angiotensina , Sistema Renina-Angiotensina/genética , Hipertensión/genética , Hipertensión/metabolismo , Animales , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Angiotensinógeno/genética , Angiotensinógeno/metabolismo , Enzima Convertidora de Angiotensina 2/genética , Enzima Convertidora de Angiotensina 2/metabolismo , Receptor de Angiotensina Tipo 1/genética , Receptor de Angiotensina Tipo 1/metabolismo , Peptidil-Dipeptidasa A/genética , Peptidil-Dipeptidasa A/metabolismo , Citocromo P-450 CYP11B2/genética , Citocromo P-450 CYP11B2/metabolismoRESUMEN
Hypertension is a disease associated with epigenetic aging. However, the pathogenic mechanism underlying this relationship remains unclear. We aimed to characterize the shared genetic architecture of hypertension and epigenetic aging, and identify novel risk loci. Leveraging genome-wide association studies (GWAS) summary statistics of hypertension (129,909 cases and 354,689 controls) and four epigenetic clocks (N = 34,710), we investigated genetic architectures and genetic overlap using bivariate casual mixture model and conditional/conjunctional false discovery rate methods. Functional gene-sets pathway analyses were performed by functional mapping and gene annotation (FUMA) protocol. Hypertension was polygenic with 2.8 K trait-influencing genetic variants. We observed cross-trait genetic enrichment and genetic overlap between hypertension and all four measures of epigenetic aging. Further, we identified 32 distinct genomic loci jointly associated with hypertension and epigenetic aging. Notably, rs1849209 was shared between hypertension and three epigenetic clocks (HannumAge, IEAA, and PhenoAge). The shared loci exhibited a combination of concordant and discordant allelic effects. Functional gene-set analyses revealed significant enrichment in biological pathways related to sensory perception of smell and nervous system processes. We observed genetic overlaps with mixed effect directions between hypertension and all four epigenetic aging measures, and identified 32 shared distinct loci with mixed effect directions, 25 of which were novel for hypertension. Shared genes enriched in biological pathways related to olfaction.
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Envejecimiento , Epigénesis Genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Hipertensión , Humanos , Hipertensión/genética , Envejecimiento/genética , Polimorfismo de Nucleótido Simple , Herencia Multifactorial/genética , Sitios Genéticos , Sitios de Carácter CuantitativoRESUMEN
OBJECTIVE: To assess the role of the systolic blood pressure polygenic risk score (SBP-PRS) in antihypertensive treatment initiation and its comparative efficacy with coronary artery calcium (CAC) scores. PATIENTS AND METHODS: This retrospective cohort study included participants with whole genome sequencing data who underwent CAC scanning between 1971 and 2008, were free of prevalent cardiovascular disease (CVD), and were not taking antihypertensive medications. The cohort was stratified by blood pressure (BP) treatment group and SBP-PRS (low/intermediate, first and second tertiles; high, third tertile) and CAC score (0 vs >0) subgroups. The primary outcome was the first occurence of adjudicated coronary heart disease, heart failure, or stroke during 10-year follow-up. The 10-year number needed to treat (NNT) to prevent 1 event of the primary outcome was estimated. A relative risk reduction of 25% for the primary outcome based on the treatment effect of intensive control (SBP <120 mm Hg) of hypertension in SPRINT (Systolic Blood Pressure Intervention Trial) was used for estimating the NNT. RESULTS: Among the 5267 study participants, the median age was 59 years (interquartile range, 51-68 years); 2817 (53.5%) were women and 2880 (54.7%) were non-White individuals. Among 1317 individuals with elevated BP/low-risk stage 1 hypertension not recommended treatment, the 10-year incidence rate of the primary outcome was 5.6% for low/intermediate SBP-PRS and 6.3% for high SBP-PRS with NNTs of 63 and 59, respectively. Similarly, the 10-year incidence rate of the primary outcome was 2.9% for CAC score 0 and 9.7% for CAC score greater than 0, with NNTs of 117 and 37, respectively. CONCLUSION: Including genetic information in risk estimation of individuals with elevated BP/low-risk stage 1 hypertension has modest value in the initiation of antihypertensive therapy. Genetic risk and CAC both have efficacy in personalizing antihypertensive therapy.
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Antihipertensivos , Enfermedad de la Arteria Coronaria , Hipertensión , Humanos , Femenino , Persona de Mediana Edad , Masculino , Antihipertensivos/uso terapéutico , Hipertensión/tratamiento farmacológico , Hipertensión/genética , Hipertensión/epidemiología , Estudios Retrospectivos , Anciano , Enfermedad de la Arteria Coronaria/genética , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Medicina de Precisión/métodos , Calcificación Vascular/genética , Calcificación Vascular/epidemiología , Medición de Riesgo , Presión Sanguínea/efectos de los fármacos , Factores de Riesgo , Predisposición Genética a la Enfermedad , Vasos Coronarios/diagnóstico por imagen , Estudios de CohortesRESUMEN
BACKGROUND: Clinical observational study demonstrated that hypertension is an independent risk factor for stroke. Furthermore, both hypertension and stroke exhibit genetic predispositions. However, the genetic relationship between hypertension and stroke in first-degree relatives remains unclear. METHOD: The Genetic effects were validated using an across-Mendelian randomization (MR) approach. The Genome-Wide Association Study summary data used in this study were obtained from a publicly available platform. The primary MR effect employed was inverse-variance weighted (IVW), and the other analysis methods included MR-Egger, weighted median, simple mode, and weighted mode. Prior to MR analysis, tests for MR_PRESSO, pleiotropy, and heterogeneity were conducted. RESULT: The presence of family history of hypertension significantly contributed to the genetic predisposition to various types of stroke, including ischemic stroke, subarachnoid hemorrhage, lacunar stroke, cardioembolic ischemic stroke, small vessel ischemic stroke, and large artery atherosclerosis-related ischemic stroke. CONCLUSION: Briefly, hypertension in first-degree relatives has a genetic impact on the risk of stroke development. Shared genetic factors may exist between hypertension and stroke.
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Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Herencia , Hipertensión , Análisis de la Aleatorización Mendeliana , Accidente Cerebrovascular , Humanos , Hipertensión/genética , Hipertensión/epidemiología , Hipertensión/fisiopatología , Hipertensión/diagnóstico , Factores de Riesgo , Accidente Cerebrovascular/genética , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Medición de Riesgo , Fenotipo , Linaje , Polimorfismo de Nucleótido Simple , Presión Sanguínea/genética , Bases de Datos GenéticasRESUMEN
Objective. Genetic factors substantially contribute to the development and duration of arterial hypertension. The study of the A1166C polymorphism of the angiotensin II type 1 receptor gene (AGTR1) in arterial hypertension is an auspicious area for assessing the relationship between heredity, hypertension development, and adipokines, but it still remains debatable. The purpose of the current study was to investigate serum adipokines levels depending on the AGTR1 A1166C polymorphism. Methods. A total of 86 patients with arterial hypertension were examined, who underwent the evaluation of the allelic A1166C polymorphism of AGTR1 by polymerase chain reaction with electrophoretic detection and determination of serum adipokines levels using enzyme-linked immunosorbent assay. Results. In the group of patients with arterial hypertension, a significant increase in serum adipokines (resistin, adiponectin, and leptin) levels was found against the background of a decrease in the antianorexic hormone ghrelin with a predominance of CC genotype carriers compared with AA genotype carriers of the AGTR1. A statistically significant decrease in ghrelin and an increase in serum adipokines (resistin, adiponectin, and leptin) in CC genotype carriers compared with AA genotype carriers of the AGTR1 were found suggesting that CC genotype carriers may be predictors of the development of arterial hypertension in our patients. Conclusions. Statistically significant decrease in ghrelin and increase in serum adipokines (resistin, adiponectin, and leptin) were found in CC genotype carriers compared with AA genotype carriers of the AGTR1, which suggests that carriers of the CC genotype are predictors of the arterial hypertension development in our patients.
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Adipoquinas , Hipertensión , Receptor de Angiotensina Tipo 1 , Humanos , Receptor de Angiotensina Tipo 1/genética , Femenino , Masculino , Hipertensión/genética , Hipertensión/sangre , Persona de Mediana Edad , Adipoquinas/sangre , Adipoquinas/genética , Adulto , Leptina/sangre , Leptina/genética , Polimorfismo de Nucleótido Simple , Adiponectina/sangre , Adiponectina/genética , Anciano , Ghrelina/genética , Ghrelina/sangre , Genotipo , Predisposición Genética a la Enfermedad , Resistina/genética , Resistina/sangreRESUMEN
OBJECTIVE: This study aimed to explore the potential role of CYP3A5 (c. 6986A>G) gene polymorphism in predicting kidney function impairment in patients with hypertension who did not have elevated serum cystatin C. METHODS: We recruited a group of patients with hypertension who did not have elevated cystatin C and analyzed the CYP3A5 (c. 6986A>G) gene polymorphism. Chi-square tests were used to compare the clinical characteristics and genotypic distribution between the two groups. Logistic regression analysis was used to explore the association between CYP3A5 (c.6986A>G) gene polymorphism and renal function impairment in hypertension with non-elevated cystatin. RESULTS: In patients with hypertension who participated in the study, there was a significant association between CYP3A5 (c. 6986A>G) gene polymorphism and kidney function impairment (p < 0.05). Patients with the CYP3A5 (c. 6986A>G) mutation display a greater risk of kidney function impairment. CONCLUSION: CYP3A5 (c. 6986A>G) gene AA homozygote polymorphism significantly increases risk of kidney function impairment in patients with hypertension with normal cystatin C. However, further studies are needed to validate this association and to further understand the mechanism of CYP3A5 (c. 6986A>G) gene polymorphism in kidney function impairment in patients with hypertension.
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Biomarcadores , Cistatina C , Citocromo P-450 CYP3A , Predisposición Genética a la Enfermedad , Hipertensión , Riñón , Polimorfismo de Nucleótido Simple , Humanos , Citocromo P-450 CYP3A/genética , Masculino , Femenino , Persona de Mediana Edad , Hipertensión/genética , Hipertensión/fisiopatología , Hipertensión/diagnóstico , Cistatina C/sangre , Cistatina C/genética , Biomarcadores/sangre , Factores de Riesgo , Riñón/fisiopatología , Fenotipo , Estudios de Asociación Genética , Homocigoto , Adulto , Anciano , Enfermedades Renales/genética , Enfermedades Renales/diagnóstico , Enfermedades Renales/sangre , Enfermedades Renales/fisiopatología , Enfermedades Renales/enzimología , Frecuencia de los Genes , Estudios de Casos y Controles , Medición de RiesgoRESUMEN
BACKGROUND: Association of asthma with the risk of cardiovascular disease has not been fully elucidated. So, this study tried to explore the genetic effect of asthma on five cardiovascular diseases and 90 peripheral cardiovascular proteins to answer the above topic. METHODS: Instrumental variables predicting asthma was extracted from its genome-wide association study data. Two-sample and multivariate MR approaches were used to assess the genetic association of exposure factor (i.e., asthma) with outcome factors (i.e., hypertension, atrial fibrillation, angina pectoris, myocardial infarction, heart failure, and 90 peripheral cardiovascular proteins). RESULTS: First, asthma nominally increased the risk of hypertension and atrial fibrillation (OR = 1.009, 95%CI = 1.003-1.016, P = 0.004; OR = 1.074, 95%CI = 1.024-1.127, P = 0.003). Second, of the 90 cardiovascular proteins, asthma was associated with the increased levels of tumor necrosis factor ligand superfamily member 14 and CC motif chemokine 4 (ß = 0.145, 95%CI = 0.077-0.212, P = 2.936e-05; ß = 0.128, 95%CI = 0.063-0.193, P = 1.036e-04). Third, CC motif chemokine 4 increased the risk of hypertension (P = 0.043); and after adjusting for this protein, asthma still increased the risk of hypertension, but the strength of its P-value changed from 0.004 to 0.011. CONCLUSION: Asthma was a risk factor for hypertension and atrial fibrillation at the genetic level, and CC motif chemokine 4 might play a mediating role in the mechanism by which asthma promoted hypertension. Thus, effective control of asthma may help reduce the risk of some cardiovascular diseases in older adults.
Asunto(s)
Asma , Enfermedades Cardiovasculares , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Humanos , Asma/genética , Asma/epidemiología , Enfermedades Cardiovasculares/genética , Fibrilación Atrial/genética , Hipertensión/genética , Factores de Riesgo , Predisposición Genética a la Enfermedad , Masculino , FemeninoRESUMEN
Background: Depression ranks as a leading contributor to the global disease burden. The potential causal relationship between the use of antihypertensive medications and depression has garnered significant interest. Despite extensive investigation, the nature of this relationship remains a subject of ongoing debate. Therefore, this study aims to evaluate the influence of antihypertensive medications on depression by conducting a Mendelian randomization study focused on drug targets. Method: We focused on the targets of five antihypertensive drug categories: ACE Inhibitors (ACEIs), Angiotensin II Receptor Antagonists (ARBs), Calcium Channel Blockers (CCBs), Beta-Blockers (BBs), and Thiazide Diuretics (TDs). We collected single-nucleotide polymorphisms (SNPs) associated with these drug targets from genome-wide association study (GWAS) statistics, using them as proxies for the drugs. Subsequently, we conducted a Mendelian randomization (MR) analysis targeting these drugs to explore their potential impact on depression. Results: Our findings revealed that genetic proxies for Beta-Blockers (BBs) were associated with an elevated risk of depression (OR [95%CI] = 1.027 [1.013, 1.040], p < 0.001). Similarly, genetic proxies for Calcium Channel Blockers (CCBs) were linked to an increased risk of depression (OR [95%CI] = 1.030 [1.009, 1.051], p = 0.006). No significant associations were identified between the genetic markers of other antihypertensive medications and depression risk. Conclusion: The study suggests that genetic proxies associated with Beta-Blockers (BBs) and Calcium Channel Blockers (CCBs) could potentially elevate the risk of depression among patients. These findings underscore the importance of considering genetic predispositions when prescribing these medications, offering a strategic approach to preventing depression in susceptible individuals.