gwas acei

Recent reports indicate a potential oncogenic role of antihypertensive drugs in common cancers. However, it remains uncertain whether this phenomenon influences the risk of glioblastoma multiforme (GBM). This study aimed to assess the potential causal effects of blood pressure (BP) and antihypertensive drugs on GBM. Genome-wide association study (GWAS) summary statistics for systolic blood pressure (SBP), diastolic blood pressure (DBP), and GBM in Europeans were downloaded. To represent the effects of antihypertensive drugs, we utilized single nucleotide polymorphisms (SNPs) associated with SBP/DBP adjacent to the coding regions of different antihypertensive drugs as instrumental variables to model five antihypertensive drugs, including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, β-receptor blockers (BBs), and thiazide diuretics...

Background: Observational investigations have provided conflicting results regarding the effect of antihypertensive drugs on the risk of COVID-19 outcomes. We intended to assess the causal effect of antihypertensive drugs on COVID-19 outcomes using drug-target Mendelian randomization (MR), mainly including angiotensin-converting enzyme inhibitors (ACEIs), β-blockers (BBs) and calcium channel blockers (CCBs). Methods: We used the genetic variants (minor allele frequency >1%, r 2 < 0.30) located within 100 k bases of each drug target gene and associated with lower systolic blood pressure ( p < 5 × 10-8 ) as genetic proxies for antihypertensive drugs...

INTRODUCTION: Observational studies suggest that different classes of antihypertensive drugs may have different effects on the occurrence of intracranial aneurysms (IA) and subarachnoid hemorrhage (SAH). However, the reported results in previous studies are inconsistent, and randomized data are absent. We performed a two-sample Mendelian randomization (MR) analysis to study the causal effects of genetically determined blood pressure (BP) and genetic proxies for antihypertensive drug classes on the risk of IA and SAH...

STUDY DESIGN: Mendelian randomization (MR) study. OBJECTIVE: To examine whether antihypertensive medications (beta-blockers, calcium channel blockers, and angiotensin-converting enzyme [ACE] inhibitors) and statins can be repurposed to prevent or treat spinal pain (back or neck pain). SUMMARY OF BACKGROUND DATA: Observational studies and a recent MR study have found associations between elevated blood pressure and greater risk of back pain...

BACKGROUND: Observational studies suggest an association between blood pressure (BP) and functional outcomes in ischemic stroke patients but whether this is causal or due to confounding is uncertain. We used Mendelian randomization (MR) to assess causality, and also explore whether particular classes of anti-hypertensives were associated with a better outcome after ischemic stroke. METHODS: We selected genetic variants associated with systolic and diastolic BP and BP-lowering variants in genes encoding antihypertensive drugs from genome-wide association studies (GWAS) on 757,601 individuals...

BACKGROUND: Associations between blood pressure (BP) with age at onset of Huntington's disease (HD) have reported inconsistent findings. We used Mendelian randomization (MR) to assess effects of BP and lowering systolic BP (SBP) via the genes encoding targets of antihypertensive drugs on age at onset of HD. METHODS: Genetic variants from genome-wide association studies(GWAS) of BP traits and BP-lowering variants in genes encoding antihypertensive drugs targets were extracted...

Background: Evidence from observational studies concerning the causal role of blood pressure (BP) and antihypertensive medications (AHM) on Parkinson's disease (PD) remains inconclusive. A two-sample Mendelian randomization (MR) study was performed to evaluate the unconfounded association of genetic proxies for BP and first-line AHMs with PD. Methods: Instrumental variables (IV) from the genome-wide association study (GWAS) for BP traits were used to proxy systolic BP (SBP), diastolic BP, and pulse pressure...

PURPOSE: For decades, Dr. John Moulder has been a leading radiation biologist and one of the few who consistently supported the study of normal tissue responses to radiation. His meticulous modeling and collaborations across the field have offered a prime example of how research can be taken from the bench to the bedside and back, with the ultimate goal of providing benefit to patients. Much of the focus of John's work was on mitigating damage to the kidney, whether as the result of accidental or deliberate clinical exposures...

PURPOSE: Pelvic radiotherapy (RT) can cause debilitating bladder toxicities but few clinical interventions exist to prevent injury or alleviate symptoms. From a large GWAS in prostate cancer patients it was previously reported that SNPs tagging AGT, part of the renin-angiotensin system (RAS), correlated with patient-reported late hematuria identifying a potential targetable pathway to prevent RT-induced bladder injury. To investigate this association, we performed a pre-clinical study to determine if RAS modulation protected the bladder against RT injury...

BACKGROUND: It is unclear whether the main antihypertensive medication classes (diuretics, calcium channel blockers, beta-blockers, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers (ARBs)) are associated with different risks of cognitive decline. Published evidence is conflicting and stems mainly from observational studies. OBJECTIVE: To investigate the differential effects of antihypertensives on the risks of developing dementia and cognitive decline, with a specific focus on the vascular component of the mechanisms underlying these interactions...

AIMS: To search for sequence variants associated with ACEi discontinuation and to test their association with ACEi-associated adverse drug reactions (ADRs). METHODS AND RESULTS: A genome-wide association study (GWAS) on ACEi discontinuation was conducted, including 33 959 ACEi-discontinuers and 44 041 controls. Cases were defined as persons who switched from an ACEi treatment to an angiotensin receptor blocker. Controls were defined as persons who continued ACEi treatment for at least 1 year...

PURPOSE: Angiotensin-converting enzyme inhibitors (ACEIs) are medications generally prescribed for patients with high cardiovascular risk; however, they are suboptimally used due to frequent adverse events (AEs). The present study aimed to identify and replicate the genetic variants associated with ACEI-related AEs in the Korean population. MATERIALS AND METHODS: A two-stage approach employing genome-wide association study (GWAS)-based discovery and replication through target sequencing was used...

BACKGROUND: Epidemiological studies have reported conflicting findings on the potential adverse effects of long-term antihypertensive medication use on cancer risk. Naturally occurring variation in genes encoding antihypertensive drug targets can be used as proxies for these targets to examine the effect of their long-term therapeutic inhibition on disease outcomes. METHODS AND FINDINGS: We performed a mendelian randomization analysis to examine the association between genetically proxied inhibition of 3 antihypertensive drug targets and risk of 4 common cancers (breast, colorectal, lung, and prostate)...

BACKGROUND AND PURPOSE: Genome-wide association studies (GWAS) of late hematuria following prostate cancer radiotherapy identified single nucleotide polymorphisms (SNPs) near AGT, encoding angiotensinogen. We tested the hypothesis that patients taking angiotensin converting enzyme inhibitors (ACEi) have a reduced risk of late hematuria. We additionally tested genetically-defined hypertension. MATERIALS AND METHODS: Prostate cancer patients undergoing potentially-curative radiotherapy were enrolled onto two multi-center observational studies, URWCI (N = 256) and REQUITE (N = 1,437)...

PURPOSE/OBJECTIVE(S): Genome-wide association studies (GWAS) identified single nucleotide polymorphisms (SNPs) near AGT associated with late hematuria following radiotherapy (RT) for prostate cancer. AGT encodes angiotensinogen and, in pre-clinical models, angiotensin pathway inhibition protects against late radiation toxicity in some tissues. Effects on the bladder have not been investigated. We tested the hypothesis that angiotensin converting enzyme inhibitors (ACEi) reduce risk of late hematuria following RT...

The 2021 Annual Review Issue of The Journal of Pathology contains 14 invited reviews on current research areas of particular importance in pathology. The subjects included here reflect the broad range of interests covered by the journal, including both basic and applied research fields but always with the aim of improving our understanding of human disease. This year, our reviews encompass the huge impact of the COVID-19 pandemic, the development and application of biomarkers for immune checkpoint inhibitors, recent advances in multiplexing antigen/nucleic acid detection in situ, the use of genomics to aid drug discovery, organoid methodologies in research, the microbiome in cancer, the role of macrophage-stroma interactions in fibrosis, and TGF-β as a driver of fibrosis in multiple pathologies...

BACKGROUND: There has been uncertainty about the safety or benefit of angiotensin-converting enzyme (ACE) inhibitors during the COVID-19 pandemic. We used Mendelian randomization using genetic determinants of serum-ACE levels to test whether decreased ACE levels increase susceptibility to SARS-CoV-2 infection or COVID-19 severity, while reducing potential bias from confounding and reverse causation in observational studies. METHODS: Genetic variants strongly associated with ACE levels, which were nearby the ACE gene, were identified from the ORIGIN trial and a separate genome-wide association study (GWAS) of ACE levels from the AGES cohort...

Angioedema occurring in the head and neck region is a rare and sometimes life-threatening adverse reaction to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). Few studies have investigated the association of common variants with this extreme reaction, but none have explored the combined influence of rare variants yet. Adjudicated cases of ACEI-induced angioedema (ACEI-AE) or ARB-induced angioedema (ARB-AE) and controls were recruited at five different centers. Sequencing of 1,066 samples (408 ACEI-AE, ARB-AE, and 658 controls) was performed using exome-enriched sequence data...

A large fraction of the adult population is on lifelong medication for cardiovascular disorders, but the metabolic consequences are largely unknown. This study determines the effects of common anti-hypertensive and lipid lowering drugs on circulating plasma protein biomarkers. We studied 425 proteins in plasma together with anthropometric and lifestyle variables, and the genetic profile in a cross-sectional cohort. We found 8406 covariate-protein associations, and a two-stage GWAS identified 17253 SNPs to be associated with 109 proteins...

OBJECTIVES: To identify single nucleotide polymorphisms (SNPs) associated with switching from an angiotensin-converting enzyme (ACE)-inhibitor to an angiotensin receptor blocker. METHODS: Two cohorts of patients starting ACE-inhibitors were identified within the Rotterdam Study in the Netherlands and the Genetics of Diabetes Audit and Research in Tayside Scotland study in Scotland. Cases were intolerant patients who switched from an ACE-inhibitor to an angiotensin receptor blocker and controls were individuals who used ACE-inhibitors continuously for at least 2 years and did not switch...