摘要
背景:虽然血管紧张素转换酶降解淀粉样蛋白-β,但血管紧张素转换酶抑制剂(ACEis)可通过胆碱能作用,增加脑物质P和提高脑啡肽酶活性以及通过调节葡萄糖体内平衡和增加分泌的脂肪因子增强阿尔茨海默病痴呆(AD)患者的胰岛素敏感性。我们旨在调查ACE基因多态性rs1800764和rs4291是否与AD患者的认知和功能改变相关,同时考虑到APOE单倍型和ACEis抗高血压治疗的分层。 方法:对连续发作的迟发型AD患者进行认知测试筛查,同时询问护理人员的功能和护理人员负担分数。考虑到APOE和ACE基因型和单倍型,以及用ACEis治疗,预测药物遗传学相关性估计为一年。 结果:193例患者中,在Hardy-Weinberg平衡中,rs1800764 - C(44.6%杂合子)和rs4291 - T(38.9%杂合子)的次要等位基因频率分别为0.497和0.345。几乎94%的患者使用胆碱酯酶抑制剂,155例(80.3%)患有动脉高血压,124例使用ACEis。对任何基因型或药物治疗没有功能影响。无论是对于包括rs1800764-T和rs4291-A在内的ACE单倍型携带者,还是对于rs1800764-T或rs4291-T的APOE4携带者,ACE都可以独立于血压变异而减缓认知下降。 APOE4 +携带者对ACEis治疗无反应。 结论:ACE可能减缓AD患者的认知功能下降,对于特定ACE基因型的APOE4携带者更为显着。
关键词: 阿尔茨海默病,痴呆,药物疗法,神经退行性疾病,神经精神病学,药物遗传学,肾素血管紧张素系统
Current Alzheimer Research
Title:Pharmacogenetics of Angiotensin-Converting Enzyme Inhibitors in Patients with Alzheimer's Disease Dementia
Volume: 15 Issue: 4
关键词: 阿尔茨海默病,痴呆,药物疗法,神经退行性疾病,神经精神病学,药物遗传学,肾素血管紧张素系统
摘要: Background: While the angiotensin-converting enzyme degrades amyloid-β, angiotensinconverting enzyme inhibitors (ACEis) may slow cognitive decline by way of cholinergic effects, by increasing brain substance P and boosting the activity of neprilysin, and by modulating glucose homeostasis and augmenting the secretion of adipokines to enhance insulin sensitivity in patients with Alzheimer’s disease dementia (AD). We aimed to investigate whether ACE gene polymorphisms rs1800764 and rs4291 are associated with cognitive and functional change in patients with AD, while also taking APOE haplotypes and anti-hypertensive treatment with ACEis into account for stratification.
Methods: Consecutive late-onset AD patients were screened with cognitive tests, while their caregivers were queried for functional and caregiver burden scores. Prospective pharmacogenetic correlations were estimated for one year, considering APOE and ACE genotypes and haplotypes, and treatment with ACEis.
Results: For 193 patients, minor allele frequencies were 0.497 for rs1800764 – C (44.6% heterozygotes) and 0.345 for rs4291 – T (38.9% heterozygotes), both in Hardy-Weinberg equilibrium. Almost 94% of all patients used cholinesterase inhibitors, while 155 (80.3%) had arterial hypertension, and 124 used ACEis. No functional impacts were found regarding any genotypes or pharmacological treatment. Either for carriers of ACE haplotypes that included rs1800764 – T and rs4291 – A, or for APOE4- carriers of rs1800764 – T or rs4291 – T, ACEis slowed cognitive decline independently of blood pressure variations. APOE4+ carriers were not responsive to treatment with ACEis.
Conclusion: ACEis may slow cognitive decline for patients with AD, more remarkably for APOE4- carriers of specific ACE genotypes.
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Cite this article as:
Pharmacogenetics of Angiotensin-Converting Enzyme Inhibitors in Patients with Alzheimer's Disease Dementia, Current Alzheimer Research 2018; 15 (4) . https://dx.doi.org/10.2174/1567205014666171016101816
DOI https://dx.doi.org/10.2174/1567205014666171016101816 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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