Search citation statements
Paper Sections
Citation Types
Year Published
Publication Types
Relationship
Authors
Journals
N Context.-Acute hypotensive transfusion reactions are potentially harmful adverse effects of transfusion attributable to bradykinin generation. They are most often seen in patients taking angiotensin-converting enzyme (ACE) inhibitors (ACE-Is) because of the role ACE plays in metabolizing bradykinin. However, a number of acute hypotensive transfusion reactions occur in patients not taking ACE-Is. Aminopeptidase P (APP), another important enzyme responsible for bradykinin degradation, is encoded by the polymorphic XPNPEP2 gene. Some polymorphisms in XPNPEP2 have been associated with decreased APP activity. However, the role that APP polymorphisms play in acute hypotensive transfusion reactions has never been investigated.Objective.-To develop a molecular assay to examine for the C-2399A single-nucleotide polymorphism (SNP) in the APP gene, XPNPEP2, in patients experiencing acute hypotensive transfusion reactions unassociated with ACEIs.Design.-We developed an assay using polymerase chain reaction and DNA sequencing with primers targeted at XPNPEP2 (59-GAGTATTATGTGGGGACCATCC-39 and 59-ATGCCTCGCAGAGACAAGAG-39). Polymorphism zygosity was determined by comparing the sense/antisense sequencing results. This assay was then applied to patients with acute hypotensive transfusion reactions not taking ACE-Is (n = 4).Results.-A C-2399A SNP assay was successfully developed and applied to patients with acute hypotensive transfusion reactions. In a pilot study, 2 patients (50%) were found to possess C-2399A polymorphisms. One was found to be homozygous, and the other was heterozygous.Conclusions.-Our C-2399A SNP assay can be used to study acute hypotensive transfusion reactions in patients not taking ACE-Is. Initial data indicate that the C-2399A polymorphism may be a contributing factor in such reactions. However, further studies are necessary to better define the role of APP polymorphisms in relation to acute hypotensive transfusion reactions unassociated with ACEIs.(Arch Pathol Lab Med. 2013;137:96-99; doi: 10.5858/ arpa.2011-0466-OA) A cute hypotensive transfusion reactions are relatively rare, but potentially serious adverse events in which a transfusion recipient manifests a marked decrease in blood pressure with a virtual absence of other signs and symptoms.1,2 Much of the pathophysiology of acute hypotensive transfusion reactions has been linked to bradykinins and their metabolites, mediators that can induce substantial vasodilation and smooth muscle relaxation in vivo, with a resultant decrease in blood pressure.3 Some studies have also shown that bradykinin accumulation and hypotensive episodes may be exacerbated in transfused patients taking angiotensin-converting enzyme (ACE) inhibitors (ACE-Is), because ACE is a key enzyme in the degradation of bradykinin.3-11 However, based on reports of acute hypotensive transfusion reactions occurring in the absence of ACE-I use, 5,12 it is possible that other pathways may contribute to the accumulation of bradykinin and/or their metabolites and result in hypotension in the se...
N Context.-Acute hypotensive transfusion reactions are potentially harmful adverse effects of transfusion attributable to bradykinin generation. They are most often seen in patients taking angiotensin-converting enzyme (ACE) inhibitors (ACE-Is) because of the role ACE plays in metabolizing bradykinin. However, a number of acute hypotensive transfusion reactions occur in patients not taking ACE-Is. Aminopeptidase P (APP), another important enzyme responsible for bradykinin degradation, is encoded by the polymorphic XPNPEP2 gene. Some polymorphisms in XPNPEP2 have been associated with decreased APP activity. However, the role that APP polymorphisms play in acute hypotensive transfusion reactions has never been investigated.Objective.-To develop a molecular assay to examine for the C-2399A single-nucleotide polymorphism (SNP) in the APP gene, XPNPEP2, in patients experiencing acute hypotensive transfusion reactions unassociated with ACEIs.Design.-We developed an assay using polymerase chain reaction and DNA sequencing with primers targeted at XPNPEP2 (59-GAGTATTATGTGGGGACCATCC-39 and 59-ATGCCTCGCAGAGACAAGAG-39). Polymorphism zygosity was determined by comparing the sense/antisense sequencing results. This assay was then applied to patients with acute hypotensive transfusion reactions not taking ACE-Is (n = 4).Results.-A C-2399A SNP assay was successfully developed and applied to patients with acute hypotensive transfusion reactions. In a pilot study, 2 patients (50%) were found to possess C-2399A polymorphisms. One was found to be homozygous, and the other was heterozygous.Conclusions.-Our C-2399A SNP assay can be used to study acute hypotensive transfusion reactions in patients not taking ACE-Is. Initial data indicate that the C-2399A polymorphism may be a contributing factor in such reactions. However, further studies are necessary to better define the role of APP polymorphisms in relation to acute hypotensive transfusion reactions unassociated with ACEIs.(Arch Pathol Lab Med. 2013;137:96-99; doi: 10.5858/ arpa.2011-0466-OA) A cute hypotensive transfusion reactions are relatively rare, but potentially serious adverse events in which a transfusion recipient manifests a marked decrease in blood pressure with a virtual absence of other signs and symptoms.1,2 Much of the pathophysiology of acute hypotensive transfusion reactions has been linked to bradykinins and their metabolites, mediators that can induce substantial vasodilation and smooth muscle relaxation in vivo, with a resultant decrease in blood pressure.3 Some studies have also shown that bradykinin accumulation and hypotensive episodes may be exacerbated in transfused patients taking angiotensin-converting enzyme (ACE) inhibitors (ACE-Is), because ACE is a key enzyme in the degradation of bradykinin.3-11 However, based on reports of acute hypotensive transfusion reactions occurring in the absence of ACE-I use, 5,12 it is possible that other pathways may contribute to the accumulation of bradykinin and/or their metabolites and result in hypotension in the se...
Disturbances in the form of microduplications and microdeletions have been found throughout the genome and have been associated with autism, intellectual disability, and recognizable malformation syndromes. In our study of 187 probands with autism, we have identified a duplication in Xq25 including full gene duplication of OCRL and six flanking genes. Activity of the enzyme gene product in fibroblasts was elevated to over twice the level in control fibroblasts. The boy had no somatic or neurological findings reminiscent of Lowe syndrome.
Pharmacogenetics in cardiovascular medicine brings the potential for personalized therapeutic strategies that improve efficacy and reduce harm. Studies evaluating the impact of genetic variation on pharmacologic effects have been undertaken for most major cardiovascular drugs, including antithrombotic agents, β-adrenergic receptor blockers, statins, and angiotensin-converting enzyme inhibitors. Across these drug classes, many polymorphisms associated with pharmacodynamic, pharmacokinetic, or surrogate outcomes have been identified. However, their impact on clinical outcomes and their ability to improve clinical practice remains unclear. This review will examine the current clinical evidence supporting pharmacogenetic testing in cardiovascular medicine, provide clinical guidance based on the current evidence, and identify further steps needed to determine the utility of pharmacogenetics in cardiovascular care. IntroductionPharmacologic effects can vary significantly between individuals, leading to reduced drug efficacy, decreased adherence, or increased adverse events. Identifying individuals who are at risk for poor therapeutic responses may be useful for amending treatment decisions to optimize benefit and minimize harm. 1 Many factors influence the effectiveness of a given pharmacologic agent, including adherence, pharmacologic and environmental interactions, and genetic effects. 2 Genetic markers have been proposed as stratification tools to predict therapeutic effects, such that pharmacologic regimens are tailored to specific genetic profiles to maximize efficacy and minimize harm. Although this approach could herald an innovative departure from current clinical cardiology practice, significant limitations in the current literature exist that make the realization of this practice difficult. This review will evaluate the clinical evidence examining pharmacogenetics in the management of cardiovascularThe authors have no funding, financial relationships, or conflicts of interest to disclose.(CV) disease (CVD) across major drug classes. We will focus on common drugs used for the treatment of CVD and thrombosis: warfarin, aspirin, clopidogrel, β-blockers, statins, and angiotensin-converting enzyme (ACE) inhibitors (ACEis). Moreover, based on the current evidence, we will provide clinical guidance regarding the current use of pharmacogenetic testing in CVD and outline future directions in research. Warfarin ResponseWarfarin is among the most effective agents to prevent thromboembolic events in patients with atrial fibrillation. However, the efficacy of warfarin is highly dependent on achieving and maintaining a narrow therapeutic window (usually an international normalized ratio [INR] between 2 and 3). Through the inhibition of vitamin K epoxide reductase complex 1 (VKORC1), warfarin limits the generation of the vitamin K hydroquinone, a necessary cofactor to sustain vitamin K-dependent coagulation factors II, VII, IX, and X. 3 Metabolism of warfarin to its inactive metabolites occurs through the cytochrome p450 ...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.