Novel polymorphisms associated with hyperalphalipoproteinemia and apparent cardioprotection

Oates, Connor P.; Koenig, Darya; Rhyne, Jeffrey; Bogush, Nikolay; O’Connell, Jeffrey R.; Mitchell, Braxton D.; Miller, Michael

doi:10.1016/j.jacl.2017.10.021

Cited by 9 publications

(12 citation statements)

References 32 publications

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“…Beside the known candidate genes of primary HALP, other genes (such APOA1, LCAT, APOA4, APOE, PLTP and PON1) involved in HDL metabolism have been reported to modulate HDL-C plasma levels [ 117 , 118 , 119 ]. Although several genes have been discovered to be associated with HDL metabolism, to date, only a small percentage of this genetic variability can be explained and their effects on HDL phenotypes should be further investigated and probably related to environmental factors [ 120 , 121 ]. Further genetic variants will be identified; therefore, it will be possible to predict, through an allelic risk score, subjects at high cardiovascular risk and possible strategies for prevention [ 122 ].…”

Section: Primary Causes Of Halpmentioning

confidence: 99%

Hyperalphalipoproteinemia and Beyond: The Role of HDL in Cardiovascular Diseases

Giammanco

Noto

Barbagallo

et al. 2021

Life

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Hyperalphalipoproteinemia (HALP) is a lipid disorder characterized by elevated plasma high-density lipoprotein cholesterol (HDL-C) levels above the 90th percentile of the distribution of HDL-C values in the general population. Secondary non-genetic factors such as drugs, pregnancy, alcohol intake, and liver diseases might induce HDL increases. Primary forms of HALP are caused by mutations in the genes coding for cholesteryl ester transfer protein (CETP), hepatic lipase (HL), apolipoprotein C-III (apo C-III), scavenger receptor class B type I (SR-BI) and endothelial lipase (EL). However, in the last decades, genome-wide association studies (GWAS) have also suggested a polygenic inheritance of hyperalphalipoproteinemia. Epidemiological studies have suggested that HDL-C is inversely correlated with cardiovascular (CV) risk, but recent Mendelian randomization data have shown a lack of atheroprotective causal effects of HDL-C. This review will focus on primary forms of HALP, the role of polygenic inheritance on HDL-C, associated risk for cardiovascular diseases and possible treatment options.

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Section: Primary Causes Of Halpmentioning

confidence: 99%

Hyperalphalipoproteinemia and Beyond: The Role of HDL in Cardiovascular Diseases

Giammanco

Noto

Barbagallo

et al. 2021

Life

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“…Funções da lipoproteína de alta densidade O HDL participa do transporte reverso de colesterol (RCT), processo no qual cristais de colesterol são removidos dos tecidos periféricos e conduzidos para o fígado, local no qual serão metabolizados sem serem descartados do corpo (Hancock-Cerutti, et al, 2017). Além disso, a HDL possui papel antiaterogênico, anti-inflamatório, anti-trombótico e antioxidante (Oates, et al, 2018).…”

Section: Resultsunclassified

“…A análise do gene inclui tanto a codificação das regiões de íntron e éxons, quanto das regiões promotoras, uma vez que analisado todas as extensões gênicas é possível observar a expressão fenotípica em indivíduos que possuem HALP e diferenciar daqueles que não expressam os genes mutados (Oates, et al, 2018).…”

Section: Mutaçõesunclassified

Hiperalfalipoproteinemia: uma revisão de literatura

Rodrigues

Martins²,

Silvério³

2022

RSD

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Objetivo: Analisar e abordar as causas e as alterações relacionadas à hiperalfalipoproteinemia, tendo como comparação os padrões gerais da população. Metodologia: Realizou-se uma Revisão de Literatura Integrativa, na qual utilizou palavras chaves especificadas nas bases de dados Pubmed e Science Direct: “hyperalphalipoprotenemia” OUR “hyperalphalipoprotein” OUR “HDLc”. Resultados: Pode-se destacar as mutações em indivíduos com hiperalfalipoproteinemia os polimorfismos de nucleotídeo único, genes deletérios, gene que expressa o CETP, deleção de SR-BI hepático, gene da lipase endotelial (EL), defeito de splicing, genes e proteínas ANGPTL3 e ANGPTL8. Além disso, foram notadas alterações na fluidez superficial e constituintes da membrana do HDLc, alteração no processo de RCT e na capacidade de aumentar a expressão e por ativar a síntese endotelial do óxido nítrico (NO). Ademais, as alterações causadas por deficiência na CETP não podem ser relacionadas a um efeito cardioprotetor, antiaterogênico e anti inflamatório, sendo até encontrada uma relação em forma de U entre o HDLc plasmático e as alterações eletrocardiográficas isquêmicas, onde a deficiência de CETP se acumula. Outrossim, presença da variante P376L, intervêm negativamente no processamento de SR-BI. Por fim, indivíduos que apresentam níveis mais elevados HDLc, exibem partículas de colesterol enriquecidas por apolipoproteínas, as quais acarretam alterações a ação anti-inflamatória do próprio HDL. Conclusão: Alterações no funcionamento fisiológico do HDLc, que provocam a hiperalfalipoproteinemia, são causadas por diversas mutações que levam a alterações no mecanismo de membrana, CETP, SR-BI e processos inflamatórios. Faz-se necessárias mais pesquisas para concluir a respeito do efeito cardioprotetor.

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“…Variation in the RXRG gene may contribute to genetic dyslipidemia in FCHL subjects [59]. UGT1A3 serves as potential therapeutic targets for CHD risk and has an effect on the function of high-density lipoprotein [60]. PPARA is an important gene that controls lipid metabolism.…”

Section: Discussionmentioning

confidence: 99%

Using Network Pharmacology to Explore Potential Treatment Mechanism for Coronary Heart Disease Using Chuanxiong and Jiangxiang Essential Oils in Jingzhi Guanxin Prescriptions

Tai

Zou

Zhang

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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Background To predict the active components and potential targets of traditional Chinese medicine and to determine the mechanism behind the curative effect of traditional Chinese medicine, a multitargeted method was used. Jingzhi Guanxin prescriptions expressed a high efficacy for coronary heart disease (CHD) patients of which essential oils from Chuanxiong and Jiangxiang were confirmed to be the most important effective substance. However, the interaction between the active components and the targets for the treatment of CHD has not been clearly explained in previous studies. Materials and Methods Genes associated with the disease and the treatment strategy were searched from the electronic database and analyzed by Cytoscape (version 3.2.1). Protein-protein interaction network diagram of CHD with Jiangxiang and Chuanxiong essential oils was constructed by Cytoscape. Pathway functional enrichment analysis was executed by clusterProfiler package in R platform. Results 121 ingredients of Chuanxiong and Jiangxiang essential oils were analyzed, and 393 target genes of the compositions and 912 CHD-related genes were retrieved. 15 coexpression genes were selected, including UGT1A1, DPP4, RXRA, ADH1A, RXRG, UGT1A3, PPARA, TRPC3, CYP1A1, ABCC2, AHR, and ADRA2A. The crucial pathways of occurrence and treatment molecular mechanism of CHD were analyzed, including retinoic acid metabolic process, flavonoid metabolic process, response to xenobiotic stimulus, cellular response to xenobiotic stimulus, cellular response to steroid hormone stimulus, retinoid binding, retinoic acid binding, and monocarboxylic acid binding. Finally, we elucidate the underlying role and mechanism behind these genes in the pathogenesis and treatment of CHD. Conclusions Generally speaking, the nodes in subnetwork affect the pathological process of CHD, thus indicating the mechanism of Jingzhi Guanxin prescriptions containing Chuanxiong and Jiangxiang essential oils in the treatment of CHD.

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Novel polymorphisms associated with hyperalphalipoproteinemia and apparent cardioprotection

Abstract: Novel functional polymorphisms in 8 candidate genes are associated with HALP in the absence of CHD. Future study is required to examine the extent to which these genes may affect HDL function and serve as potential therapeutic targets for CHD risk reduction.

Cited by 9 publications

References 32 publications

Hyperalphalipoproteinemia and Beyond: The Role of HDL in Cardiovascular Diseases

Hyperalphalipoproteinemia and Beyond: The Role of HDL in Cardiovascular Diseases

Hiperalfalipoproteinemia: uma revisão de literatura

Using Network Pharmacology to Explore Potential Treatment Mechanism for Coronary Heart Disease Using Chuanxiong and Jiangxiang Essential Oils in Jingzhi Guanxin Prescriptions

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