Fabricio Ferreira de Oliveira, Sandro Soares de Almeida, Elizabeth Suchi Chen, Paulo Henrique Ferreira Bertolucci, Marilia Cardoso Smith
{"title":"一项前瞻性观察性研究：阿尔茨海默病患者对他汀类药物的反应中选择的遗传变异和脂质谱变异性之间的关系","authors":"Fabricio Ferreira de Oliveira, Sandro Soares de Almeida, Elizabeth Suchi Chen, Paulo Henrique Ferreira Bertolucci, Marilia Cardoso Smith","doi":"10.1590/1516-3180.2024.0160.27112024","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Lipid profiles are largely determined by genetic variants, and lipid metabolism plays a crucial role in Alzheimer's disease.</p><p><strong>Objective: </strong>To investigate whether lipid profile variability in response to diverse statins could be affected by cholesterol metabolism-related genetic variants in Alzheimer's disease..</p><p><strong>Design and setting: </strong>This prospective observational pharmacogenetic study was conducted at the Universidade Federal de São Paulo (Unifesp), Brazil.</p><p><strong>Methods: </strong>Consecutive outpatients were prospectively followed for lipid profile variations over one year, estimated by the associations between statin therapy and the following variants: rs2695121 (NR1H2), rs3846662 (HMGCR), rs11669576 (LDLR8), rs5930 (LDLR10), rs5882 and rs708272 (CETP), rs7412 and rs429358 (APOE), and ACE insertion/deletion polymorphism.</p><p><strong>Results: </strong>All polymorphisms in the 189 patients were in Hardy-Weinberg equilibrium. Statins resulted in lower total cholesterol and LDL cholesterol levels, whereas the effects on HDL cholesterol varied according to the statin used. Atorvastatin resulted in lower triglyceride level variations than simvastatin. APOE-ε4 carriers showed a better response to atorvastatin in elevating HDL-cholesterol than APOE-ε4 non-carriers. Carriers of the ACE insertion allele had cumulatively lower total cholesterol and LDL-cholesterol levels, regardless of statin therapy, but lower triglyceride levels when using atorvastatin. Carriers of rs11669576-G had lower total cholesterol and LDL-cholesterol levels when using simvastatin, and lower total cholesterol and triglycerides when using atorvastatin. Concerning CETP haplotypes, carriers of rs5882-A and rs708272-A benefitted the most from statins, which lowered total cholesterol and increased HDL-cholesterol levels, and from atorvastatin lowering triglycerides; however, the effects of atorvastatin lowering total cholesterol and LDL-cholesterol were more pronounced for carriers of rs5882-GG/rs708272-GG.</p><p><strong>Conclusion: </strong>Lipid profile variations may be pharmacogenetically mediated in Alzheimer's disease, thus, confirming their high heritability.</p>","PeriodicalId":49574,"journal":{"name":"Sao Paulo Medical Journal","volume":"143 4","pages":"e2024160"},"PeriodicalIF":1.6000,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12356643/pdf/","citationCount":"0","resultStr":"{\"title\":\"Associations between selected genetic variants and lipid profile variability in response to statins in Alzheimer's disease: a prospective observational study.\",\"authors\":\"Fabricio Ferreira de Oliveira, Sandro Soares de Almeida, Elizabeth Suchi Chen, Paulo Henrique Ferreira Bertolucci, Marilia Cardoso Smith\",\"doi\":\"10.1590/1516-3180.2024.0160.27112024\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Lipid profiles are largely determined by genetic variants, and lipid metabolism plays a crucial role in Alzheimer's disease.</p><p><strong>Objective: </strong>To investigate whether lipid profile variability in response to diverse statins could be affected by cholesterol metabolism-related genetic variants in Alzheimer's disease..</p><p><strong>Design and setting: </strong>This prospective observational pharmacogenetic study was conducted at the Universidade Federal de São Paulo (Unifesp), Brazil.</p><p><strong>Methods: </strong>Consecutive outpatients were prospectively followed for lipid profile variations over one year, estimated by the associations between statin therapy and the following variants: rs2695121 (NR1H2), rs3846662 (HMGCR), rs11669576 (LDLR8), rs5930 (LDLR10), rs5882 and rs708272 (CETP), rs7412 and rs429358 (APOE), and ACE insertion/deletion polymorphism.</p><p><strong>Results: </strong>All polymorphisms in the 189 patients were in Hardy-Weinberg equilibrium. Statins resulted in lower total cholesterol and LDL cholesterol levels, whereas the effects on HDL cholesterol varied according to the statin used. Atorvastatin resulted in lower triglyceride level variations than simvastatin. APOE-ε4 carriers showed a better response to atorvastatin in elevating HDL-cholesterol than APOE-ε4 non-carriers. Carriers of the ACE insertion allele had cumulatively lower total cholesterol and LDL-cholesterol levels, regardless of statin therapy, but lower triglyceride levels when using atorvastatin. Carriers of rs11669576-G had lower total cholesterol and LDL-cholesterol levels when using simvastatin, and lower total cholesterol and triglycerides when using atorvastatin. Concerning CETP haplotypes, carriers of rs5882-A and rs708272-A benefitted the most from statins, which lowered total cholesterol and increased HDL-cholesterol levels, and from atorvastatin lowering triglycerides; however, the effects of atorvastatin lowering total cholesterol and LDL-cholesterol were more pronounced for carriers of rs5882-GG/rs708272-GG.</p><p><strong>Conclusion: </strong>Lipid profile variations may be pharmacogenetically mediated in Alzheimer's disease, thus, confirming their high heritability.</p>\",\"PeriodicalId\":49574,\"journal\":{\"name\":\"Sao Paulo Medical Journal\",\"volume\":\"143 4\",\"pages\":\"e2024160\"},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2025-08-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12356643/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Sao Paulo Medical Journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1590/1516-3180.2024.0160.27112024\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, GENERAL & INTERNAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Sao Paulo Medical Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1590/1516-3180.2024.0160.27112024","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
Associations between selected genetic variants and lipid profile variability in response to statins in Alzheimer's disease: a prospective observational study.
Background: Lipid profiles are largely determined by genetic variants, and lipid metabolism plays a crucial role in Alzheimer's disease.
Objective: To investigate whether lipid profile variability in response to diverse statins could be affected by cholesterol metabolism-related genetic variants in Alzheimer's disease..
Design and setting: This prospective observational pharmacogenetic study was conducted at the Universidade Federal de São Paulo (Unifesp), Brazil.
Methods: Consecutive outpatients were prospectively followed for lipid profile variations over one year, estimated by the associations between statin therapy and the following variants: rs2695121 (NR1H2), rs3846662 (HMGCR), rs11669576 (LDLR8), rs5930 (LDLR10), rs5882 and rs708272 (CETP), rs7412 and rs429358 (APOE), and ACE insertion/deletion polymorphism.
Results: All polymorphisms in the 189 patients were in Hardy-Weinberg equilibrium. Statins resulted in lower total cholesterol and LDL cholesterol levels, whereas the effects on HDL cholesterol varied according to the statin used. Atorvastatin resulted in lower triglyceride level variations than simvastatin. APOE-ε4 carriers showed a better response to atorvastatin in elevating HDL-cholesterol than APOE-ε4 non-carriers. Carriers of the ACE insertion allele had cumulatively lower total cholesterol and LDL-cholesterol levels, regardless of statin therapy, but lower triglyceride levels when using atorvastatin. Carriers of rs11669576-G had lower total cholesterol and LDL-cholesterol levels when using simvastatin, and lower total cholesterol and triglycerides when using atorvastatin. Concerning CETP haplotypes, carriers of rs5882-A and rs708272-A benefitted the most from statins, which lowered total cholesterol and increased HDL-cholesterol levels, and from atorvastatin lowering triglycerides; however, the effects of atorvastatin lowering total cholesterol and LDL-cholesterol were more pronounced for carriers of rs5882-GG/rs708272-GG.
Conclusion: Lipid profile variations may be pharmacogenetically mediated in Alzheimer's disease, thus, confirming their high heritability.
期刊介绍：
Published bimonthly by the Associação Paulista de Medicina, the journal accepts articles in the fields of clinical health science (internal medicine, gynecology and obstetrics, mental health, surgery, pediatrics and public health). Articles will be accepted in the form of original articles (clinical trials, cohort, case-control, prevalence, incidence, accuracy and cost-effectiveness studies and systematic reviews with or without meta-analysis), narrative reviews of the literature, case reports, short communications and letters to the editor. Papers with a commercial objective will not be accepted.
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