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1.
J Oral Pathol Med ; 49(1): 82-90, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31402483

RESUMO

BACKGROUND: Progressive telomere shortening with age or chronic inflammation may lead to genomic instability that characterizes the early stage of carcinogenesis. Certain risk factors, such as drinking alcoholic beverages or smoking, predispose the oral mucosa to squamous cell carcinoma. The ADH1B and ALDH2 genotypes can influence the risk of cancer due to alcohol drinking. In the present study, we analyzed chromosomal instability due to telomere shortening in the oral mucosa in relation to cancer risk factors. DESIGN: Using our quantitative fluorescence in situ hybridization (Q-FISH) technique, we estimated telomere lengths (TL) in the background mucosa from 23 cases of mucosal carcinoma, 12 cases of oral epithelial dysplasia, and 21 non-neoplasia cases. ALDH2 and ADH1B genotypes were determined using DNA extracted from paraffin sections. We analyzed TL in relation to alcohol drinking, smoking, and cancer multiplicity. RESULTS: Telomeres in the backgrounds of dysplasia and mucosal carcinoma were significantly shorter than in controls. In comparison with adult controls, telomeres were significantly (P = .038) shorter in the ADH1B less-active type (ADH1B*1/*1), but not (P = .841) in the ALDH2 inactive type (ALDH2*1/*2 or *2/*2). Cancer multiplicity and smoking had no significant relationship with TL. CONCLUSION: Telomeres in the oral epithelium are shorter in cases of oral dysplasia or mucosal carcinoma than in non-neoplasia. Unlike the esophageal epithelium of alcoholics, they are also shorter in individuals with the less-active rather than the active ADH1B gene. Telomeres in the oral epithelium may be directly affected by alcohol drinking.


Assuntos
Álcool Desidrogenase/genética , Aldeído-Desidrogenase Mitocondrial/genética , Encurtamento do Telômero , Adulto , Consumo de Bebidas Alcoólicas , Genótipo , Humanos , Hibridização in Situ Fluorescente , Polimorfismo Genético
2.
Fa Yi Xue Za Zhi ; 35(5): 576-580, 2019 Oct.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-31833292

RESUMO

Abstract: Objective To explore the change rules of blood ethanol and blood acetaldehyde concentration, the impairment of psychomotor functions of different acetaldehyde dehydrogenase (ALDH) 2 genotype individuals after alcohol consumption and the relationship among them. Methods The ALDH2 genotypes in seventy-nine healthy volunteers were obtained by SNaPshotTM method, then divided into ALDH2*1/*1 (wild type) and ALDH2*1/*2 (mutant type) group. After volunteers consumed 1.0 g/kg of alcohol, blood ethanol concentration and blood acetaldehyde concentration at a series of time points before and after alcohol consumption and psychomotor functions, such as, visual selective response time, auditory simple response time and tracking experiment were detected. Biphasic alcohol response questionnaires were collected. Results After alcohol consumption, ALDH2*1/*2 group's blood ethanol and blood acetaldehyde concentration reached the peak earlier than ALDH2*1/*1 group. Its blood acetaldehyde concentration was higher than that of ALDH2*1/*1 group, 1-6 h after alcohol consumption. The psychomotor functions, such as visual selective response time and auditory simple response time in ALDH2*1/*2 group were more significantly impaired than those in ALDH2*1/*1 group after alcohol consumption. There was no statistical significance between the two groups in excitement or sedation reactions (P>0.05). Pearson correlation coefficient test showed that blood acetaldehyde concentration was related with psychomotor function. Conclusion There are significant differences between the psychomotor function of ALDH2 wild type and mutant type individuals after alcohol consumption estimated to be related to the difference in blood acetaldehyde concentration after alcohol consumption.


Assuntos
Acetaldeído/sangue , Consumo de Bebidas Alcoólicas , Aldeído Desidrogenase/genética , Etanol/metabolismo , Polimorfismo Genético/genética , Desempenho Psicomotor/efeitos dos fármacos , Acetaldeído/metabolismo , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/sangue , Aldeído-Desidrogenase Mitocondrial , Aldeído Oxirredutases , Etanol/administração & dosagem , Etanol/sangue , Genótipo , Humanos , Desempenho Psicomotor/fisiologia
3.
Life Sci ; 239: 117015, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31678551

RESUMO

Obstructive renal injury and drug-induced nephrotoxicity are the two most common causes of renal fibrosis diseases. However, whether these two different pathogeny induced same pathological outcomes contain common genetic targets or signaling pathway, the current research has not paid great attention. GSE121190 and GSE35257 were downloaded from the Gene Expression Omnibus (GEO) database. While GSE121190 represents a differential expression profile in kidney of mice with unilateral ureteral obstruction (UUO) model, GSE35257 represents cisplatin nephrotoxicity model. By using GEO2R, 965 differential expression genes (DEGs) in GSE121190 and 930 DEGs in GSE35257 were identified. 43 co-DEGs were shared and were extracted for protein-protein interaction (PPI) analysis. Subsequently, three shared pathways including glycolysis/gluconeogenesis, fatty acid degradation and pathways in cancer were involved in two models with Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. We reconfirmed that these three pathways have relatively high scores by using Gene Set Enrichment Analysis (GSEA) software. Additionally, further bioinformatic analysis showed that Aldehyde dehydrogenase-2 (Aldh2) involved in the progression of renal fibrosis by mediating glycolysis pathway. Then real-time PCR and western blotting were performed to validate the expression of Aldh2 in kidney tissue after three different etiologies that caused renal fibrosis. Basically consistent with our bioinformatics results, our experiment showed that the expression of Aldh2 is the most significantly decreased in the UUO model, followed by ischemia-reperfusion injury (IRI) model and finally the cisplatin-induced model. Thus, Aldh2 can act as a common potential genetic target for different renal fibrosis diseases.


Assuntos
Aldeído-Desidrogenase Mitocondrial/genética , Nefropatias/tratamento farmacológico , Nefropatias/enzimologia , Aldeído-Desidrogenase Mitocondrial/efeitos dos fármacos , Animais , Cisplatino/toxicidade , Biologia Computacional , Bases de Dados Genéticas , Fibrose , Redes Reguladoras de Genes/efeitos dos fármacos , Redes Reguladoras de Genes/genética , Nefropatias/induzido quimicamente , Nefropatias/genética , Camundongos , Camundongos Endogâmicos BALB C , Mapas de Interação de Proteínas , Obstrução Ureteral/complicações , Obstrução Ureteral/genética , Obstrução Ureteral/patologia
4.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(5): 737-742, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31762247

RESUMO

OBJECTIVE: To establish SNaPShot-fluorescence capillary analysis (SNaPShot-FCA) assay for rapid detection of the genotype of aldehyde dehydrogenase 2 gene (ALDH2) rs671 locus. METHODS: The genomic DNA was extracted from peripheral blood cells. Using R6G-ddATP and cy5-ddGTP as fluorescent substrates, the ALDH2 gene was amplified by SNaPShot to generate DNA products with different fluorescent dyes at the 3' end. FCA was used to detect the products separated by agarose gel electrophoresis and recovered by gel recovery kit, and the genetype of ALDH2 polymorphism was analyzed by fluorescence spectrum. The samples were tested three times repeatedly and compared with the results of DNA sequencing. RESULTS: The optimal concentrations of R6G-ddATP and cy5-ddGTP were 1.4 µmol/L and 8.0 µmol/L, respectively. 106 samples were tested for ALDH2 genotype by SNaPShot-FCA under optimal conditions, including 67 of wild type (GG), 38 of hybrid type (AG), and 1 of mutant type (AA), which were consistent with the sequencing results. CONCLUSION: This study successfully established the SNaPShot-FCA for the micro-detection of ALDH2 genotype for the rapid screening and identification of ALDH2 gene.


Assuntos
Aldeído-Desidrogenase Mitocondrial/genética , Genótipo , Análise de Sequência de DNA/métodos , Fluorescência , Humanos
5.
Biomed Res Int ; 2019: 2476252, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31467875

RESUMO

Severe hemorrhagic shock and resuscitation (HS/R) can lead to lung injury, resulting in respiratory insufficiency. We investigated whether treatment with Alda-1, an ALDH2 activator, decreased lung injury induced by severe HS/R in a rat model. Male Sprague-Dawley rats were randomized into three groups, hemorrhagic shock + placebo, hemorrhagic shock + Alda-1, and sham. All animals were heparinized, and then 50% of the total calculated blood volume was collected over 60 minutes. After 40 minutes of hemorrhagic shock, animals were reinfused with the shed blood over 40 minutes and then observed for an additional 2 hours. Concentrations of 4-HNE, TNF-α, IL-6, and ALDH2 activity were detected; lung injury and lung wet-to-dry weight ratios were assessed. Expression of occludin and ZO-1 proteins in lung tissues was also determined. At 2 hours after resuscitation, lung injury was significantly reduced and the wet-to-dry weight ratio was notably decreased in the Alda-1 group compared with placebo (P<0.05). Alda-1 treatment also significantly increased the activity of ALDH2 and decreased the levels of toxic 4-HNE (P<0.05). In the Alda-1 group, IL-6 and TNF-α were dramatically decreased compared with placebo-treated animals (P<0.05). Expression of occludin and ZO-1 proteins was significantly decreased in the placebo group compared with the Alda-1 group (P<0.05). Thus, in a rat model of severe HS/R, treatment with Alda-1 increased the activity of ALDH2, significantly accelerated the clearance of reactive aldehydes, and concomitantly alleviated lung injury through improvement of pulmonary epithelial barrier integrity resulting in decreased alveolar epithelial tissue permeability, lung edema, and diffuse infiltration of inflammatory cells.


Assuntos
Aldeídos/metabolismo , Benzamidas/farmacologia , Benzodioxóis/farmacologia , Lesão Pulmonar/tratamento farmacológico , Pulmão/efeitos dos fármacos , Choque Hemorrágico/tratamento farmacológico , Aldeído-Desidrogenase Mitocondrial/genética , Animais , Modelos Animais de Doenças , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Epitélio/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Pulmão/metabolismo , Pulmão/patologia , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Ocludina/genética , Ratos , Choque Hemorrágico/genética , Choque Hemorrágico/patologia , Fator de Necrose Tumoral alfa/genética , Proteína da Zônula de Oclusão-1/genética
6.
Yakugaku Zasshi ; 139(8): 1111-1119, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31366848

RESUMO

A new single nucleotide polymorphisms (SNP) genotyping method has been developed and validated using biological specimens directly as templates for TaqMan PCR without general DNA extraction and purification procedure from dried saliva samples attached on water-soluble papers. This new method can set up at ease and complete PCR analysis including data interpretation in under two hours with additional advantages of application for large-scale clinical research, diagnostics, and epidemiological studies at low cost. Specifically, SNP genotyping of alcohol metabolism-related genes ADH1B (rs1229984) and ALDH2 (rs671) were demonstrated by TaqMan PCR assay using dried saliva samples in the present investigation. In this protocol, by simplifying experimental operations and improving efficiency, omitting and simplifying the time and laborious DNA purification process, it is possible to shorten the experiment time and reduce the risk of human error such as contamination. Furthermore it became possible with great cost reduction. We succeeded in dramatically improving the judgment rate and accuracy of SNP genotyping by the master mix reagent for commercial available real-time TaqMan PCR. Moreover, it becomes possible to stably introduce template DNA into the reaction system, and it will be possible to apply it to copy number variation (CNV) by TaqMan probe method. The SNP analysis process using this optimized water-soluble paper will be applied to gene polymorphism analysis of drug metabolizing enzyme gene CYP, etc., to help efforts to realize personalized medicine.


Assuntos
Álcool Desidrogenase/genética , Álcoois/metabolismo , Aldeído-Desidrogenase Mitocondrial/genética , Genótipo , Técnicas de Genotipagem/métodos , Polimorfismo de Nucleotídeo Único/genética , Variações do Número de Cópias de DNA , Humanos , Reação em Cadeia da Polimerase em Tempo Real , Saliva
7.
Adv Exp Med Biol ; 1193: 35-52, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31368096

RESUMO

Aldehydes, which are present within the air as well as food and beverage sources, are highly reactive molecules that can be cytotoxic, mutagenic, and carcinogenic. To prevent harm from reactive aldehyde exposure, the enzyme aldehyde dehydrogenase 2 (ALDH2) metabolizes reactive aldehydes to a less toxic form. However, the genetic variant of ALDH2, ALDH2*2, significantly reduces the ability to metabolize reactive aldehydes in humans. Therefore, frequent environmental aldehyde exposure, coupled with inefficient aldehyde metabolism, could potentially lead to an increased health risk for diseases such as cancer or cardiovascular disease.Here, we discuss the environmental sources of reactive aldehydes and the potential health implications particularly for those with an ALDH2*2 genetic variant. We also suggest when considering the ALDH2*2 genetic variant the safety limits of reactive aldehyde exposure may have to be reevaluated. Moreover, the ALDH2*2 genetic variant can also be used as an example for how to implement precision medicine in the field of environmental health sciences.


Assuntos
Aldeído-Desidrogenase Mitocondrial/genética , Aldeídos/efeitos adversos , Exposição Ambiental/efeitos adversos , Humanos
8.
Adv Exp Med Biol ; 1193: 53-67, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31368097

RESUMO

Aldehyde dehydrogenase 2 (ALDH2) is a non-cytochrome P450 mitochondrial aldehyde oxidizing enzyme. It is best known for its role in the metabolism of acetaldehyde, a common metabolite from alcohol drinking. More evidences have been accumulated in recent years to indicate a greater role of ALDH2 in the metabolism of other endogenous and exogenous aldehydes, especially lipid peroxidation-derived reactive aldehyde under oxidative stress. Many cardiovascular diseases are associated with oxidative stress and mitochondria dysfunction. Considering that an estimated 560 million East Asians carry a common ALDH2 deficient variant which causes the well-known alcohol flushing syndrome due to acetaldehyde accumulation, the importance of understanding the role of ALDH2 in these diseases should be highlighted. There are several unfavorable cardiovascular conditions that are associated with ALDH2 deficiency. This chapter reviews the function of ALDH2 in various pathological conditions of the heart in relation to aldehyde toxicity. It also highlights the importance and clinical implications of interaction between ALDH2 deficiency and alcohol drinking on cardiovascular disease among the East Asians.


Assuntos
Acetaldeído/efeitos adversos , Consumo de Bebidas Alcoólicas , Aldeído-Desidrogenase Mitocondrial/genética , Doenças Cardiovasculares/genética , Grupo com Ancestrais do Continente Asiático , Humanos
9.
Adv Exp Med Biol ; 1193: 69-87, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31368098

RESUMO

Despite the role of aldehyde dehydrogenase 2 (ALDH2) in the detoxification of endogenous aldehydes, the defective polymorphism (rs671), which is highly prevalent among East Asians, does not show a serious phenotype, such as congenital abnormality. However, unfavorable and favorable impacts of the variant allele, ALDH2*2, on various disease risks have been reported. The underlying mechanisms are often complicated due to the compensatory aldehyde detoxification systems. As the phenotypes emerge due to overlapping environmental factors (e.g., alcohol intake and tobacco smoke) or individual vulnerabilities (e.g., aging and apolipoprotein E ε4 allele), polymorphism is therefore considered to be important in the field of preventative medicine. For example, it is important to recognize that ALDH2*2 carriers are at a high risk of alcohol drinking-related cancers; however, their drinking habit has less adverse effects on physiological indices, such as blood pressure, body mass index, levels of lipids, and hepatic deviation enzymes in the blood, than in non-ALDH2*2 carriers. Therefore, opportunities to reconsider their excessive drinking habit before adverse events occur can be missed. To perform effective disease prevention, the effects of ALDH2*2 on various diseases and the biological mechanisms should be clarified.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Aldeído-Desidrogenase Mitocondrial/genética , Polimorfismo Genético , Alelos , Grupo com Ancestrais do Continente Asiático , Humanos
10.
Adv Exp Med Biol ; 1193: 107-120, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31368100

RESUMO

Myocardial ischemia-reperfusion (IR) injury during acute myocardial infarction or open-heart surgery would promote oxidative stress, leading to the accumulation of reactive aldehydes that cause cardiac damage. It has been well demonstrated that aldehyde dehydrogenase (ALDH)-2 is an important cardioprotective enzyme for its central role in the detoxification of reactive aldehydes. ALDH2 activation by small molecule activators is a promising approach for cardioprotection for myocardial IR injury.


Assuntos
Aldeído-Desidrogenase Mitocondrial/genética , Traumatismo por Reperfusão Miocárdica/genética , Miocárdio/enzimologia , Humanos , Mitocôndrias Cardíacas , Estresse Oxidativo
11.
Adv Exp Med Biol ; 1193: 121-134, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31368101

RESUMO

Coronary spasm plays an important role in the pathogenesis of ischemic heart disease, including angina pectoris, acute myocardial infarction (AMI), silent myocardial ischemia, and sudden death. The prevalence of coronary spasm is higher among East Asians probably due to genetic as well as environmental factors. ALDH2 eliminates toxic aldehydes including 4-hydroxy-2-nonenal (4-HNE) derived from lipid peroxidation and acrolein in tobacco smoking as well as ethanol-derived acetaldehyde and thereby protects tissues and cells from oxidative damage. Deficient variant ALDH2*2 genotype is prevalent among East Asians and is a significant risk factor for both coronary spasm and AMI through accumulation of toxic aldehydes, thereby contributing to oxidative stress, endothelial damage, vasoconstriction, and thrombosis. Toxic aldehydes are thus identified as risk factors to be targeted for the treatment of coronary spasm and AMI.


Assuntos
Aldeído-Desidrogenase Mitocondrial/genética , Vasoespasmo Coronário/genética , Infarto do Miocárdio/genética , Grupo com Ancestrais do Continente Asiático , Genótipo , Humanos
12.
Adv Exp Med Biol ; 1193: 135-154, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31368102

RESUMO

Obesity is multifactorial and complex. Remarkable progress has been made recently in search for polygenic obesity through genome-wide association study (GWAS), but biology of polygenic effects on obesity is largely poor. This review summarizes the available evidence and provides an overview of the links between ALDH2 variants and adiposity, which were firstly and mainly derived from studies of polygenic obesity and also indirectly investigated by using cell lines and mice. The genetic association studies have observed consistent associations of ALDH2 variants with obesity-related traits including BMI, waist circumference (WC), waist-to-hip ratio (WHR), and visceral fat accumulation. In consideration of ALDH2 variants with enzyme activity and alcohol consumption behavior in physiological mechanism studies, we proposed a model by which the physiological and behavioral consequences of alcohol consumption serve as an intermediary process between polymorphisms in ALDH2 and obesity.


Assuntos
Aldeído-Desidrogenase Mitocondrial/genética , Obesidade/genética , Adiposidade/genética , Animais , Índice de Massa Corporal , Estudo de Associação Genômica Ampla , Humanos , Camundongos , Polimorfismo de Nucleotídeo Único , Circunferência da Cintura , Relação Cintura-Quadril
13.
Adv Exp Med Biol ; 1193: 155-174, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31368103

RESUMO

A major pathophysiological mechanism behind the development of diabetic heart diseases is oxidative stress mediated by toxic reactive aldehydes such as 4-hydroxynonenal (4HNE). Aldehyde dehydrogenase (ALDH) 2 is a mitochondrial enzyme that has been found to detoxify these deleterious aldehydes and thereby mitigate cardiac damage. Furthermore, its protective role in cellular signaling reverses aberrations caused by hyperglycemia, thereby protecting cardiac function. This chapter assesses the role of ALDH2 in diabetic heart diseases by examining preclinical studies where ALDH2 activity is perturbed in both decreased and increased directions. In doing so, issues in improving ALDH2 activity in select human populations are elucidated, and further research directions are discussed.


Assuntos
Aldeído-Desidrogenase Mitocondrial/genética , Diabetes Mellitus/genética , Cardiopatias/genética , Aldeídos/efeitos adversos , Cardiopatias/complicações , Humanos , Estresse Oxidativo
14.
Adv Exp Med Biol ; 1193: 175-194, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31368104

RESUMO

Sepsis, defined as life-threatening tissue damage and organ dysfunction caused by a dysregulated host response to infection, is a critical disease which imposes global health burden. Sepsis-induced organ dysfunction, including circulatory and cardiac dysfunction, hepatic dysfunction, renal dysfunction, etc., contributes to high mortality and long-term disability of sepsis patients. Altered inflammatory response, ROS and reactive aldehyde stress, mitochondrial dysfunction, and programmed cell death pathways (necrosis, apoptosis, and autophagy) have been demonstrated to play crucial roles in septic organ dysfunction. Unfortunately, except for infection control and supportive therapies, no specific therapy exists for sepsis. New specific therapeutic targets are highly warranted. Emerging studies suggested a role of potential therapeutic target of ALDH2, a tetrameric enzyme located in mitochondria to detoxify aldehydes, in septic organ dysfunction. In this article, we will review the presentations and pathophysiology of septic organ dysfunction, as well as summarize and discuss the recent insights regarding ALDH2 in sepsis.


Assuntos
Aldeído-Desidrogenase Mitocondrial/genética , Sepse/genética , Apoptose , Autofagia , Humanos , Mitocôndrias/enzimologia
15.
Adv Exp Med Biol ; 1193: 195-210, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31368105

RESUMO

Cerebral stroke is one of the leading causes of mortality and disability worldwide. The prevalence of cerebral stroke is the result of the synergistic effect of genetic susceptibility and numerous vascular risk factors, including hypertension, diabetes, excessive alcohol intake, obesity, and dyslipidemia. Mitochondrial aldehyde dehydrogenase (ALDH2) is a vital enzyme metabolizing various acetaldehyde and toxic aldehydes. The ALDH2 enzymatic activity is severely decreased in the individuals with ALDH2*2 gene mutation, especially in East Asians. Increasing epidemiological surveys have revealed that ALDH2 genetic polymorphism is closely associated with the increasing incidence of cardiovascular risk factors and cerebral stroke. Evidence from experimental studies has also suggested that ALDH2 facilitates the clearance of reactive aldehydes and reduces the size of cerebral infarct. Therefore, targeting ALDH2 may represent a promising avenue for protection against stroke injury. This review will mainly focus on clinical and epidemiological evidence and the underlying molecular mechanisms involved in the protective effect of ALDH2 in stroke-related injury.


Assuntos
Aldeído-Desidrogenase Mitocondrial/genética , Acidente Vascular Cerebral/genética , Predisposição Genética para Doença , Humanos , Polimorfismo Genético
16.
Adv Exp Med Biol ; 1193: 211-220, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31368106

RESUMO

Aldehyde dehydrogenase 2 (ALDH2) is an important member of the functional aldehyde dehydrogenases (ALDHs) family in human beings, playing a fundamental role in the detoxification of acetaldehyde and other aldehydes. In recent years, a number of researches have given attention to the association between ALDH2 and atherosclerosis, which provided insights on targeting ALDH2 for therapeutic intervention of atherosclerosis. In this review, these inspiring studies will be discussed, and the clinical implications and concerns will be expounded.


Assuntos
Aldeído-Desidrogenase Mitocondrial/genética , Aterosclerose/genética , Acetaldeído , Aldeídos , Humanos
17.
Adv Exp Med Biol ; 1193: 221-228, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31368107

RESUMO

Aldehyde dehydrogenase 2 (ALDH2) is a member of ALDH family. ALDH1 has been widely recognized for its roles in carcinogenesis and cancer therapy; however, investigation for ALDH2 in cancer is seldom mentioned. The ALDH2 point mutation ALDH2*2 is the most frequent human gene variant, and it is present in approximately 560 million East Asians. ALDH2*2 demonstrates its effect on alcohol consumption limiting and alcoholism developing protection, and this variant is recently found to have an important impact on human health. This chapter focuses on its potential effect on cancer therapy, especially for chemotherapeutics with anthracyclines.


Assuntos
Consumo de Bebidas Alcoólicas , Aldeído-Desidrogenase Mitocondrial/genética , Antraciclinas/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/genética , Alcoolismo/genética , Humanos
18.
Adv Exp Med Biol ; 1193: 229-236, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31368108

RESUMO

Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme in the detoxification of toxic aldehydes, especially acetaldehyde, which is commonly considered as a carcinogen. ALDH2 mutation and impaired enzymatic activity will cause acetaldehyde accumulation and thus participate in the development of cancers. It deserves more attention since around 40% of East Asian population carry the inactive ALDH2 allele. Moreover, the risk for cancers will be even higher when ALDH2 mutation combined with heavy alcohol consumption, suggesting a genetic-environmental interaction in carcinogenesis. This may provide us with a potential target for cancer prevention and treatment.


Assuntos
Consumo de Bebidas Alcoólicas , Aldeído-Desidrogenase Mitocondrial/genética , Interação Gene-Ambiente , Acetaldeído , Carcinogênese , Humanos
19.
Adv Exp Med Biol ; 1193: 237-253, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31368109

RESUMO

Aging is a complex irreversible biological process associated with increased prevalence of chronic disease and high healthcare burden. Several theories have been proposed for the biology of aging including free radical accumulation, DNA damage, apoptosis, telomere shortening, autophagy failure, and disturbed autonomic response. Aging is also closely associated with progressive deterioration of cardiovascular and neurological functions. Linkage, genome-wide association (GWAS), and next-generation sequencing analysis have confirmed a number of susceptibility loci for aging, in particular, Alzheimer's disease. Recent evidence from our group and others also revealed a tie between genetic mutation of mitochondrial aldehyde dehydrogenase (ALDH2) and life span as well as cardiovascular aging. ALDH2 represents the single most gene with the greatest number of human genetic polymorphism and is deemed an important enzyme for detoxification of reactive aldehydes. Here, we will briefly review the tie between ALDH2 and cardiovascular aging process. While recent work on ALDH2 research has broadened the pathogenic mechanisms of ALDH2 mutation or deficiency, therapeutic potential targeting ALDH2 in the elderly still remains debatable.


Assuntos
Aldeído-Desidrogenase Mitocondrial/genética , Sistema Cardiovascular , Longevidade/genética , Estudo de Associação Genômica Ampla , Humanos , Polimorfismo Genético
20.
DNA Cell Biol ; 38(9): 962-968, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31361523

RESUMO

Previous studies revealed that the rs671 polymorphism in the acetaldehyde dehydrogenase 2 (ALDH2) genes is correlated with alcohol consumption in Japanese population. The ALDH2 gene variants and drinking are associated with hypertension and dyslipidemia. However, it remains unclear whether there might be potent relationships among ALDH2 rs671 polymorphism, alcohol consumption, hypertension, and dyslipidemia in Shandong population. A total of 467 male volunteers from Shandong area were enrolled in this study. The ALDH2 rs671 polymorphism was genotyped using polymerase chain reaction-restriction fragment length polymorphism. The concentrations of total cholesterol (TC), triglycerides, low-density lipoprotein, and high-density lipoprotein (HDL) in serum were measured using commercial kits. SPSS 23.0 was used for statistical analysis. The significance of differences between subgroups was determined using chi-square test, and multiple comparisons were performed with the least-significant difference method. The ALDH2 variant frequencies were 80.5% with GG, 17.1% with GA, and 2.4% with AA. The ALDH2 genotypes had significant correlations with alcohol consumption (p = 0.001), whereas the GA genotype was associated with a decreased risk of alcohol consumption (odds ratio = 0.27; 95% confidence interval = 0.130-0.539; p = 0.001). The ALDH2 genotypes frequencies and drinking habits were significantly different between hypertension and healthy individuals (p = 0.034; p = 0.044). The ALDH2 GG genotype individuals have high average lipids levels, and the proportion of TC disorder among GG individuals was higher than that of GA individuals (p = 0.006). Individuals who had drinking habits have a high average lipids levels; especially average TC levels (p = 0.048), and had high proportions of dyslipidemia (TC and HDL; p = 0.016 and p = 0.033, respectively). The frequencies of ALDH2 variants were evaluated according to the Hardy-Weinberg equilibrium among enrolled population. Our study suggested that the individuals with ALDH2 rs671 GA genotype were less prone to developing a drinking habit in Shandong population. The ALDH2 genotypes and drinking habit were associated with hypertension and lipid profiles especially TC profile in Shandong province. The ALDH2 rs671 genotypes indicated that the gene-related drinking habit and gene variant altogether may affect hypertension and dyslipidemia.


Assuntos
Aldeído-Desidrogenase Mitocondrial/genética , Colesterol/sangue , Hipertensão/genética , Polimorfismo de Nucleotídeo Único , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , China , Humanos , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade
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