Progress on the relationship of aldehyde dehydrogenase 2 with human diseases and its small-molecule activators / 药学实践杂志

Aldehyde dehydrogenase 2 (ALDH2) is one of important factors against from the damage under oxidative stress in human body. A high proportion of East Asians carry ALDH2 inactive mutation gene. There are many diseases closely related to ALDH2, such as cardiovascular diseases, neurodegenerative diseases and liver diseases. Recent studies also have found that ALDH2 is associated with ferroptosis. Therefore, ALDH2 has becoming a potential target for the treatment of the above related diseases. Several types of small molecule activators with potential value of clinical application have been reported. The research progress on the structure and function of ALDH2 , the relationship with human diseases and its activators were summarized in this paper.

Aldehyde dehydrogenase 2 rs671 genetic polymorphisms are associated with chemotherapy-induced nausea and vomiting / 南方医科大学学报

OBJECTIVE@#To investigate the correlation between aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphisms and chemotherapy-induced nausea and vomiting (CINV).@*METHODS@#A total of 90 Chinese patients with malignant tumors receiving chemotherapy for the first time were recruited in this study. The occurrence of CINV was observed within 120 h after treatment with docetaxel and cis-platinum chemotherapy (DP regimen). The data of the patients (including age, gender, tumor stage, habitual alcohol consumption, motion sickness, morning sickness, and average sleep time prior to chemotherapy) were collected through a questionnaire. ALDH2 rs671 polymorphisms of the patients were analyzed using a multiple single nucleotide polymorphism genotyping, and the Hardy-Weinberg equation was used for genetic linkage analysis. The correlations between the factors including ALDH2 rs671 polymorphisms and the occurrence of CINV were analyzed.@*RESULTS@#The incidence of CINV was 48.9% among the patients receiving their first chemotherapy with DP regimen. Univariate analysis indicated that the genetic polymorphisms of ALDH2 rs671 were significantly correlated with the occurrence of CINV (P < 0.05). Multivariate logistic analysis indicated that ALDH2 rs671 mutation (OR: 3.019, 95% CI: 1.056-8.628, P < 0.05) and average sleep time prior to chemotherapy no longer than 6 h (OR: 2.807, 95% CI: 1.033-7.628, P < 0.05) were risk factors for CINV in patients with malignant tumors receiving the first chemotherapy with DP regimen.@*CONCLUSION@#ALDH2 gene mutation at rs671 is a risk factor contributing to the occurrence of CINV, and understanding of the underlying mechanism may help to more effectively control the occurrence of CINV.

Research progress on cold ischemia injury of steatotic donor livers / 器官移植

Liver transplantation is a vital treatment for end-stage liver disease. However, the shortage of donor livers has limited the development of liver transplantation. How to expand the source of donor livers has become a challenge in the academic community. In recent years, the proportion of donors with non-alcoholic fatty liver disease (NAFLD) has been increased. Rational use of steatotic donor livers is a feasible approach to expand the donor pool. Cold ischemia injury during donor liver preservation before liver transplantation increases the risk of postoperative organ dysfunction. Therefore, it is of significance to unravel the mechanism and intervention measures of cold ischemia injury of steatotic donor livers. Cold ischemia injury of steatotic donor livers is characterized as the damage of mitochondria, lysosomes and endoplasmic reticulum at the organelle level, and up-regulated expression of adenosine monphosphate activated protein kinase (AMPK), aldehyde dehydrogenase 2 (ALDH2) and heme oxygenase (HO)-1 at the protein level. In this article, the research progresses on cold ischemia injury of steatotic donor livers and relevant intervention measures were reviewed.

The role of ALDH2 in tumorigenesis and tumor progression: Targeting ALDH2 as a potential cancer treatment

A major mitochondrial enzyme for protecting cells from acetaldehyde toxicity is aldehyde dehydrogenase 2 (ALDH2). The correlation between ALDH2 dysfunction and tumorigenesis/growth/metastasis has been widely reported. Either low or high ALDH2 expression contributes to tumor progression and varies among different tumor types. Furthermore, the ALDH2∗2 polymorphism (rs671) is the most common single nucleotide polymorphism (SNP) in Asia. Epidemiological studies associate ALDH2∗2 with tumorigenesis and progression. This study summarizes the essential functions and potential ALDH2 mechanisms in the occurrence, progression, and treatment of tumors in various types of cancer. Our study indicates that ALDH2 is a potential therapeutic target for cancer therapy.

Injury of aldehyde dehydrogenase 2 in organ ischemia-reperfusion injury through autophagy / 中华肝胆外科杂志

With the rapid development of organ transplantation in China,the donation after cardiac death (DCD) donor organs are widely used.However,the quality of these organs is relatively poor,so the way to preserve and maintain organ still remains a severe problem.Among them,ischemic reperfusion injury (IRI) impairs the organs severely.Acetaldehyde dehydrogenase 2 (ALDH2) protects organs from stress conditions,including ischemia-reperfusion injury,and the activation and autophagy inhibition also protects the organs from stress conditions as well.Recent studies showed that ALDH2 can regulate autophagy to inhibit the organ injury during ischemia-reperfusion.Our study aims to discuss the new findings in this mechanism.

High resolution melting analysis for detection of ALDH 2 and ADH1B gene polymorphisms / 国际检验医学杂志

Objective To establish the system of high resolution melting for detection of aldehyde dehydro-genase 2(ALDH2) and alcohol dehydrogenase-1B (ADH1B) gene polymorphisms .Methods The short prim-ers were designed for ALDH2 and ADH1B gene .Different PCR products were analyzed using Eva Green dyes after amplification ,which were confirmed by Sanger sequencing .Results The genotypes of ALDH2 rs671 and ADH1B rs1229984 were successfully detected in the same procedure by HRM within 90min ,and the results were consistent with Sanger sequencing .Conclusion The assay of HRM is simple ,rapid ,cost-effective ,and re-liable for the detection of ALDH2 and ADH1B polymorphism and it is worthy to be popularized .

Effects of activation of mitochondrial aldehyde dehydrogenase 2 on MMP-14 and TIMP-4 in high glucose induced rat cardiomyocytes injury / 中国药理学通报

Aim To observe whether matrix metallo-proteinase-14 ( MMP-14) and tissue matrix metallopro-teinase inhibitor-4 ( TIMP-4) were involved in the car-diac-protection of mitochondrial aldehyde dehydrogen-ase 2 ( ALDH2) against high glucose induced rat pri-mary cardiomyocyte injury. Methods Rat primary cardiomyocytes were cultured. The cardiomyocyte via-bility was detected by MTT assay at different concentra-tion of glucose at different time point. After established high glucose-induced cardiomyocytes injury model, cardiomyocytes were randomly divided into 4 groups:normal control group ( NG, glucose at 5.5 mmol· L-1) , NG + Alda-1 group ( Alda-1 at 20 μmol·L-1) , high glucose group ( HG, glucose at 30 mmol·L-1) and HG+Alda-1 group. The cell viability at 48 h and oxidative stress level were detected by MTT and DHE staining methods. The protein expressions of ALDH2, MMP-14 and TIMP-4 were determined by Western blot. Results The cardiomyocytes injury model was established according to the cell activity result. Com-pared with NG group, the cell viability, the protein ex-pressions of ALDH2, MMP-14, the ratio of MMP-14/TIMP-4 were decreased, TIMP-4 protein expression and the level of oxidative stress were increased in HG group. Compared with HG group, in HG + Alda-1 group, the cell viability, the protein expressions of AL-DH2, MMP-14, the ratio of MMP-14/TIMP-4 were in-creased, the levels of oxidative stress and TIMP-4 pro-tein expression were decreased. Conclusion Activa-tion of mitochondrial ALDH2 may relieve high glucose induced cardiomyocytes injury. The protective effect was likely related to the inhibition of oxidative damage, down-regulation of MMP-14 and up-regulation of TIMP-4 proteins.

Relativity of gene polymorphism of aldehyde dehydrogenase 2 to premature coronary heart disease / 解放军医学杂志

Objective To investigate the relationship between aldehyde dehydrogenase 2 (ALDH2) gene polymorphism and premature coronary heart disease (CHD) in Chinese Han population.Methods A total of 505 patients were enrolled in the present study.Of them,375 were definitely diagnosed as CHD and another 130 were excluded from CHD by coronary angiography.Coronary heart disease patients were divided into premature coronary heart disease (male ＜55 years,female ＜65 years) group (n=150) and late onset coronary heart disease (male ≥ 55 years,female ≥ 65 years) group (n=225);According to whether after drinking flushing,the enrolled 505 patients were divided into alcohol flushing syndrome(AFS) group (n=135) and no AFS group (n=370);According to whether used to drinking,they were divided into accustomed to drinking group (n=189) and no drinking custom group (n=316).The ALDH2 gene polymorphism was analyzed by sanger sequencing.Results There was no significant difference in the distribution ofALDH2 genotype between the patients with premature CHD and late-onset CHD,also between CHD and non-CHD (P＞0.05).The logistic regression analysis showed that ALDH2 gene was not a predisposing factor of PCHD and CHD after adjusting for gender,age,smoking,drinking,body mass index (BMI),hypertension,diabetes,hyperlipidemia and family history of CHD (P=0.729,OR=1.098,95％CI 0.648-1.859;P=0.581,OR=1.156,95％CI 0.692-1.930).The incidence of ALDH2 mutant (GA+AA) was significantly higher in AFS group than in no AFS group (67.4％ vs.10.5％,P＜0.01).The gene mutation frequency was markedly higher in no drinking custom group than in accustomed to drinking group (29.7％ vs.19.1％,P＜0.01).Conclusions No obvious correlation exists between ALDH2 gene polymorphism and the incidence of premature CHD or the onset of CHD in Chinese Han population.There is a certain relationship between ALDH2 mutant gene and AFS.

Alcohol Consumption, Aldehyde Dehydrogenase 2 Gene Polymorphisms, and Cardiovascular Health in Korea

Alcohol consumption is a serious health issue in Korea in terms of the amount consumed and the behavior related to its consumption. Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme in alcohol metabolism that degrades acetaldehyde to nontoxic acetic acid. The enzyme is coded by the ALDH2 gene, which is commonly polymorphic in East Asian populations. A point mutation in the ALDH2 gene (the rs671 allele) yields an inactive form of ALDH2 that causes acetaldehyde accumulation in the body after alcohol consumption, thereby inhibiting normal alcohol metabolism. Individuals who are homozygous for polymorphism in ALDH2 tend to refrain from drinking alcohol, decreasing their chances of developing alcoholism and exposure to the associated risks. Mendelian randomization (MR) studies have demonstrated that alcohol consumption predicted by ALDH2 genotype is causally related to cardiovascular risks. Moreover, recent MR studies suggest that the ALDH2 variant has mechanistic effects on some disease outcomes or mortality through increased blood levels of acetaldehyde, showing differences therein between heterozygotes (ALDH2*2*2) and homozygotes (ALDH2*1*2) in those who consume alcohol. Accordingly, consideration of ALDH2 genotype in alcohol prevention programs is warranted. In conclusion, strategies that incorporate genetic information and provide an evidential basis from which to help people make informed decisions on alcohol consumption are urgently required.

Mechanism of Aldehyde Dehydrogenase-2 Regulated Human Endothelial Progenitor Cells Oxidative Stress Reaction / 中国循环杂志

Objective: To investigate the role of aldehyde dehydrogenase-2 (ALDH-2) for regulating human endothelial progenitor cells (EPCs) oxidative stress reaction and its mechanism. Methods: Human EPCs were isolated from peripheral blood of healthy adults and the cells were cultured in 4 groups:①Blank control group,②Alda-1 group, the cells were treated by 1μmol/L Alda-1, a speciifc activator of ALDH-2,③tBHP (10μg/ml) group and④Alda-1 pretreatment+tBHP group. EPCs reactive oxygen species (ROS) levels were evaluated by DCFH-DA staining, mitochondrial membrane potentials were detected by JC-1 method, migration capacity was measured by transwell chamber method and the activation of p38 signal pathway was examined by Western blot analysis. Results: Compared with Blank control group, ROS levels in tBHP group and Alda-1 pretreatment+tBHP group were (441.7 ± 24.8) % and (237.4 ± 12.0) %, allP<0.05. In Blank control group, tBHP group and Alda-1 pretreatment+tBHP group, the proportion of EPCs lost their mitochondrial membrane potentials were (5.7 ± 2.1) %, (81.7 ± 3.7) % and (37.4 ± 3.2) % respectively, allP<0.05; the number of EPCs migration were (108 ± 9)/HP, (22 ± 4)/HP and (67 ± 7)/HP respectively, allP<0.05. Compared with Blank control group, the activation of p38 signal pathway increased to (259.1 ± 7.7) % in tBHP group, while it was reduced to (186.4 ± 8.0) % in Alda-1 pretreatment+tBHP group. Conclusion: ALDH-2 could reduce ROS level in human EPCs, it may decrease mitochondrial membrane damage, protect migration which might be related to p38 signal pathway.

Detection of Single Nucleotide Polymorphism by Real-time Polymerase Chain Reaction Coupled with High Specific Invader Assay in Single Tube / 分析化学

A method for the real-time polymerase chain reaction ( PCR ) coupled with high specific invader assay to detect single nucleotide polymorphism ( SNP) was established. To reduce the background signal, the amount of flap endonuclease 1 ( FEN1 enzyme ) and wild-type detection probe was optimized. Under the optimum conditions including 0. 05 μmo/L invasive oligonucleotide probe, 0. 125 μmol/L wild-type detection probe, 0. 5 μmol/L mutation detection probe, 0. 25 μmol/L each fluorescence resonance energy transfer (FRET) probe and 1. 5 U FEN1, the background signal of wild-type sample and mutation sample was dramatically decreased and the background interference to the detecting results was thus eliminated. A total of 21 cases of aldehyde dehydrogenase-2*2 ( ALDH2*2 ) , 19 cases of cytochrome p450 2 C19*2 ( CYP2 C19*2 ) and 19 cases of CYP2C19*3 were analyzed with the established method, and the genotypes of ALDH2*2 were 10 cases of GG homozygote, 8 cases of GA heterozygote and 3 cases of AA homozygote; the genotypes of CYP2C19*2 were 9 cases of GG homozygote, 8 cases of GA heterozygote and 2 cases of AA homozygote;and the genotypes of CYP2C19*3 were 18 cases of GG homozygote and 1 case of GA heterozygote. These results were consistent with those by pyrosequencing. The established method was specific, simple, short time-consuming and low cost, and could be used for the detection of SNP genotyping with non-polluting in single closed tube.

Association of a Missense ALDH2 Single Nucleotide Polymorphism (Glu504Lys) With Benign Prostate Hyperplasia in a Korean Population / 대한배뇨장애요실금학회지

PURPOSE: Aldehyde dehydrogenase 2 (ALDH2) is a well-known gene involved in alcohol and aldehyde metabolism. Moreover, recent studies have reported associations between ALDH2 and age-related disorders. Benign prostate hyperplasia (BPH) is an age-related disorder and genetic factors may contribute to its onset. In this study, we investigated the association of a well-studied ALDH2 single nucleotide polymorphism (SNP), rs671, with the onset and clinical features of BPH. METHODS: A total of 222 BPH patients and 214 control subjects were genotyped. The clinical features of the BPH patients (prostate volume, prostate-specific antigen level, and International Prostatic Symptom Score) were analyzed. RESULTS: The results show that rs671 was only associated with the volume of BPH in genotype and allele frequencies (P<0.05). CONCLUSION: We propose that rs671 is an Asian-specific SNP in ALDH2 that may affect the disease progression of BPH in the Korean population.

Aldehyde dehydrogenase 2 mediated the protection against ischemia/reperfusion injury in renal tubular epithelial cells induced by ethanol pretreatment / 中华器官移植杂志

ObjectiveTo investigate the role of aldehyde dehydrogenase 2 (ALDH2) in the protection against tubular epithelial cells (TEC) ischemia/reperfusion (IR)injury induced by pretreatment with ethanol.Methods Mouse primary cultured TECs were pretreated with 50 mM ethanol 3 h before simulation of in vitro IR.Lactate dehydrogenase (LDH) release was assessed to evaluate the protection of ethanol pretreatment on IR injury.Thereafter,TECs were transfected with a negative control siRNA (NC) or an ALDH2-siRNA. The ALDH2 protein levels and ALDH enzymatic activities were assessed 48 h after transfection.Ethanol pretreatment and in vitro IR were performed on those transfected TECs.LDH release was assessed to evaluate the role of ALDH2 in the ethanol pretreatment-induced protection against IR injury.ResultsEthanol pretreatment significantly reduced the LDH release in TECs upon IR insult.As compared with NC group and INTERFERin group,the ALDH2 protein levels were decreased by 82.1％,ALDH enzymatic activities were decreased hy 67.3％,and the protective effect induced by ethanol pretreatment was almost completely abrogated in ALDH2-siRNA group.ConclusionEthanol pretreatment protects TECs against IR injury through ALDH2 dependent pathways.

Genetic polymorphisms of alcohol dehydrogenase-2 and aldehyde dehydrogenase-2 associated with the susceptibility on esophageal cancer / 中华流行病学杂志

Objective To evaluate the impact of alcohol dehydrogenase-2 (ADH2) and aldehyde dehydrogenase-2 (ALDH2) polymorphisms on the susceptibility of esophageal cancer. Methods A case-control study including 221 cases of esophageal cancer and 191 controls was carried out in Taixing city of Jiangsu province. ADH2 and ALDH2 genotypes were tested by PCR and denaturing high -- performance liquid chromatography (DHPLC). Results (1) Compared with ALDH2 G/G carriers, ALDH2 A/A (OR=5.69, 95%CI: 2.51-12.18) and ALDH2 G/A (OR=1.70, 95%CI: 1.08-2.68) carriers showed a significantly elevated risk of developing esophageal cancer, especially among alcohol drinkers with ALDH2 A/A (OR=8.63,95% CI: 2.07-35.95). (2) Statistical relation was not found between ADH2 genotypes and the risk of esophageal cancer, with regard to the status of alcohol consumption. (3) Whether subjects with whatever ADH2 genotype, ALDH2 G/A or A/A carriers was found to have significantly increased the risk of developing esophageal cancer, with ALDH2 A/A carriers appeared having higher esophageal cancer risk than those ALDH2 G/A carriers. (4)Compared those non-drinkers with both ALDH2 G/G and ADH2 A/A , drinkers with ALDH2 G/A or A/A and ADH2 C,/A or G/G genotypes showed a significantly elevated risk of developing esophageal cancer (OR=8.36, 95% CI: 2.98-23.46). Conclusion These results revealed that it was not ADH2 but ALDH2 polymorphisms and drinking alcohol had a significant interaction with the development of esophageal cancer, suggesting that in order to help lowering the risk of esophageal cancer, individuals who are carrying ALDH2 A/A or G/A genotypes should be encouraged to reduce their consumption of alcohols.

Blood Pressure, Levels of Serum Lipids, Liver Enzymes and Blood Glucose by Aldehyde Dehydrogenase 2 and Drinking Habit in Japanese Men

Objectives: The association of blood pressure and levels of serum lipids, liver enzymes, blood glucose and aldehyde dehydrogenase 2 (ALDH2) with drinking habit was examined in Japanese men. Methods: The subjects were 264 men aged 39 to 80 years who were classified into the ALDH2 deficiency or sufficiency group using the ethanol patch test and the Tokyo University ALDH2 Phenotype Screening Test. A self-administered questionnaire including drinking habit was used. Blood pressure and the levels of biochemical markers in groups with ALDH2 sufficiency, ALDH2 deficiency and drinking habit were compared using multiple regression models for adjusting age, smoking habit, physical exercising habit and body mass index. Results: The levels of serum high-density lipoprotein cholesterol, triglycerides, aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (γ-GTP) were significantly higher in current drinkers of 20 g of ethanol or more per day than in nondrinkers of the ALDH2 sufficiency group. The levels of serum AST and γ-GTP in current drinkers of 20 g of ethanol or more per day, and fasting blood sugar in current drinkers of less than 20 g of ethanol per day were significantly higher than those in nondrinkers of the ALDH2 deficiency group. Conclusions: These results suggest that alcohol consumption increases the levels of serum lipids and liver enzymes in ALDH2-sufficient individuals and liver enzymes and blood glucose levels in ALDH2-deficient individuals.

Blood pressure, levels of serum lipids, liver enzymes and blood glucose by aldehyde dehydrogenase 2 and drinking habit in Japanese men

<p><b>OBJECTIVES</b>The association of blood pressure and levels of serum lipids, liver enzymes, blood glucose and aldehyde dehydrogenase 2 (ALDH2) with drinking habit was examined in Japanese men.</p><p><b>METHODS</b>The subjects were 264 men aged 39 to 80 years who were classified into the ALDH2 deficiency or sufficiency group using the ethanol patch test and the Tokyo University ALDH2 Phenotype Screening Test. A self-administered questionnaire including drinking habit was used. Blood pressure and the levels of biochemical markers in groups with ALDH2 sufficiency, ALDH2 deficiency and drinking habit were compared using multiple regression models for adjusting age, smoking habit, physical exercising habit and body mass index.</p><p><b>RESULTS</b>The levels of serum high-density lipoprotein cholesterol, triglycerides, aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (γ-GTP) were significantly higher in current drinkers of 20 g of ethanol or more per day than in nondrinkers of the ALDH2 sufficiency group. The levels of serum AST and γ-GTP in current drinkers of 20 g of ethanol or more per day, and fasting blood sugar in current drinkers of less than 20 g of ethanol per day were significantly higher than those in nondrinkers of the ALDH2 deficiency group.</p><p><b>CONCLUSIONS</b>These results suggest that alcohol consumption increases the levels of serum lipids and liver enzymes in ALDH2-sufficient individuals and liver enzymes and blood glucose levels in ALDH2-deficient individuals.</p>

Role of mitochondrial aldehyde dehydrogenase 2 in postconditioning induced cardioprotection / 中国药理学通报

Aim To investigate the role of mitochondrial aldehyde dehydrogenase 2 ( ALDH2) in the cardio-protection of ischemic postconditioning in isolated rat hearts. Methods Hearts isolated from male Sprague-Dawley rats were perfused on a langendorff apparatus and subjected to 30 min of regional ischemia( occlusion of left anterior descending artery) followed by 120 min reperfusion. Ischemic postconditioning was achieved by 6 cycles of 10 s reperfusion/10 s global ischemia starting at the beginning of reperfusion. The ventricular hemodynamic parameters and lactate dehydrogenase ( LDH) release during reperfusion were measured. The infarct size was measured by TTC staining method. The expressions of ALDH2,Bcl-2 and Bax at mRNA level of left anterior myocardium were detected by RT-PCR analysis. Results In contrast to ischemia and reperfusion,ischemic postconditioning improved the recovery of left ventricular developed pressure,rate pressure product during reperfusion,and reduced LDH release and infarct size. The expressions of ALDH2 mRNA level and the ratio of Bcl-2 /Bax were increased. Adminis-tration of ALDH2 antagonist cyanamide at the beginning of reperfusion attentuated the role of ischemic postconditioning. Conclusion Ischemic postconditioning plays a role in the cardioprotection partially through increasing mitochondrial ALDH2 mRNA expression.

Distribution of genetic polymorphism of aldehyde dehydrogenase-2 (ALDH2) in Indonesian subjects.

Aldehyde dehydrogenase (ALDH) plays a pivotal role in the alcohol metabolism. Decreased activity of ALDH enzyme has more influence on the hypersensitivity to alcohol than of alcohol dehydrogenase. ALDH enzyme exists in several isozymes. Among these isozymes, ALDH2 is a major isozyme that has a very high affinity for acetaldehyde. Recent studies suggested that the deficiency of ALDH2 may be inherited. Functional polymorphism of ALDH2 gene has been observed in a nucleotide of the 487th codon. In the atypical gene, this codon consists of AAA nucleotides for lysine, instead of GAA for glutamic acid in the wild type gene. In this study, we have analyzed the genetic polymorphism of ALDH2 gene among 100 Indonesian students using genomic DNA extracted from hair roots. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods were performed for this purpose. Three oligonucleotide primers were designed for two steps PCR. The reverse primer R was intentionally constructed not to be 100% complementary to the template strand, to generate a restriction site for Eco RI within the variable nucleotide in the PCR product of ALDH2 gene. This study indicates that 70 subjects (70%) have wild type, 29 (29%) atypical heterozygote and only 1 (1%) atypical homozygote ALDH2 alleles. Conclusively, the atypical ALDH2 allele frequency in Indonesians (31/200) is higher than in Caucasoids (only about 5-10%), but less than in Mongoloids (40-50%). This may be due to the diverse ethnics of Indonesian population.

Genotyping mitochondrial aldehyde dehydrogenase-2 (ALDH2) Glu504Lys polymorphism by real time PCR / 中华检验医学杂志

Objective To develop an effective real time PCR method for genotyping mitochondrial aldehyde dehydrogenase-2(ALDH2)Glu504Lys polymorphism based on the hydrolysis probes.Methods The Mg~(2+)and probe concentration were optimized,the precision and sensitivity were also checked.The genotypings by this method were confirmed by the direct sequencing of amplified PCR products.Results The optimized Mg~(2+)and probe concentration were 2.5 mmol/L and 1.0 ?mol/L,respectively.The inter- group(n=20)and intra-group(n=20)CVs of Ct were 1.38% and 1.48 %,respectively.The method could detect human DNA in the range of 5.0?10~2-5.0 ?10~6 pg per 25 ?l reaction.The results from 150 individuals by this genotyping method are in full concordance with that by direct PCR products sequencing.Conclusion The combined merits of reliability,flexibility and simplicity should make this method suitable for routine clinical testing and cost-efficient large-scale genotyping.

Effects of Genetic Factor, Life Styles, and Diet on Urinary Hippuric Acid Excretion in Toluene Exposed Workers / 대한산업의학회지

OBJECTIVES: The purpose was to investigate the distributions and the effects of genetic polymorphism of aldehyde dehydrogenase 2(ALDH2), cytochrome P450 1A1(CYP1A1), and cytochrome P450 2E1(CYP2E1) on the toluene metabolism. METHODS: The subjects consisted of 160 workers who were exposed to toluene in different industries such as paint manufacturing, painting on steel and wood products, printing, bonding, and coating. The exposed toluene level was monitored by passive air sampler, and the questionnaire variables were age, sex, smoking, drinking, previous nights drinking, use of personal protective equipment, work duration, and taking benzoic acid containing food. The urinary hippurric acid collected in the end of shift was corrected by urinary creatinine concentration. The genotypes of ALDH2, CYP1A1, and CYP2E1 were investigated using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) methods with DNA extracted from venous blood. RESULTS: The geometric mean and the geometric standard deviation of urinary hippuric acid concentration were 0. 44 g/g creatinine and 2. 80. The urinary hippuric acid concentration was significantly related to personal exposed toluene level among personal exposed toluene level, use of personal protective equipment, and benzoic acid containing food diet. The slope differences of the regression for ALDH2, CYP1A1, and CYP2El genetic polymorphism, age, smoking, and work duration tended to be significant. In multiple regression analysis, the regression coefficient of toluene, ALDH2, CYP1A1, CYP2E1 genetic polymorphism were significant. CONCLUSIONS: Prom the above results, urinary hippuric acid level after toluene exposure was significantly affected by the genetic polymorphism of ALDH2, CYP1A1, CYP2E1. It is needed further investigation of the urinary hippuric acid level considering the effect of genetic polymorphism.