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 SNaPshot^TM 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.
Acetaldehyde/metabolism* ; Alcohol Drinking/blood* ; Aldehyde Dehydrogenase/genetics* ; Aldehyde Dehydrogenase, Mitochondrial ; Aldehyde Oxidoreductases ; Ethanol/metabolism* ; Genotype ; Humans ; Polymorphism, Genetic/genetics* ; Psychomotor Performance/physiology*

Aldehyde dehydrogenase 2 (ALDH2), as one of the most important alcohol metabolizing enzymes, plays a significant role in the detoxification process of acetaldehyde which is a main carcinogenic product of alcoholic metabolism. Alteration in its genotypes (particularly at the site of rs671) is closely associated with a variety of tumors in drinkers. Recent advance in the research of the association of the ALDH2 gene rs671 polymorphisms with cancer susceptibility in drinkers is reviewed.
Alcohol Drinking ; genetics ; Aldehyde Dehydrogenase ; genetics ; Aldehyde Dehydrogenase, Mitochondrial ; Genetic Predisposition to Disease ; Humans ; Neoplasms ; etiology ; genetics ; Polymorphism, Genetic

OBJECTIVETo investigate the correlation between drinking behavior combined with polymorphisms of extracellular superoxide dismutase (EC-SOD) and aldehyde dehydrogenase-2 (ALDH2) genes and pancreatic cancer.

METHODSThe genetic polymorphisms of EC-SOD and ALDH2 were analyzed by polymerase chain reaction restriction fragment length polymorphism in the peripheral blood leukocytes obtained from 680 pancreatic cancer cases and 680 non-cancer controls. Subsequently the frequency of genotype was compared between the pancreatic cancer patients and the healthy controls.The relationship of drinking with pancreatic cancer was analyzed.

RESULTSThe frequencies of EC-SOD (C/G) and ALDH2 variant genotypes were 37.35% and 68.82% respectively in the pancreatic cancer cases, and were significantly higher than those in the healthy controls (21.03% and 44.56%, all P<0.01). People who carried EC-SOD (C/G) (OR=2.24, 95% CI= 1.81-4.03, P<0.01) or ALDH2 variant genotypes (OR=2.75, 95% CI=1.92-4.47, P<0.01) had a high risk to develop pancreatic cancer. Those who carried EC-SOD (C/G) genotype combined with ALDH2 variant genotype had a high risk for pancreatic cancer (29.56% vs. 6.76%, OR=7.69, 95% CI=3.58-10.51, P<0.01). The drinking rate of the pancreatic cancer group (64.12%) was significantly higher than that of the control group (40.15%; OR=2.66, 95% CI=1.30-4.42, P<0.01). An interaction between drinking and EC-SOD (C/G)/ALDH2 variant genotypes increased the risk of occurrence of pancreatic cancer (OR=25.00, 95% CI= 11.87-35.64, P<0.01).

CONCLUSIONEC-SOD (C/G), ALDH2 variant genotypes and drinking might be the risk factors of pancreatic cancer.

Alcohol Drinking ; Aldehyde Dehydrogenase ; genetics ; Base Sequence ; DNA Primers ; Female ; Humans ; Male ; Middle Aged ; Pancreatic Neoplasms ; genetics ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Risk Factors ; Superoxide Dismutase ; genetics

OBJECTIVE: To explore alcohol pharmacokinetics as well as acetaldehyde level in peripheral blood in human subjects with different ALDH2 genotypes after drinking. METHODS: Venous blood samples of 14 unrelated volunteers were collected. Polymerase chain reaction-restriction fragment length polymorphism technology was adopted for DNA extraction and ALDH2 genotyping. The volunteers were asked to drink beer at certain doses. The concentration of alcohol and acetaldehyde were assayed by headspace gas chromatography method at different time. The pharmacokinetic parameters were calculated. RESULTS: According to the results of electrophoresis, 5 people carried ALDH2*1/*1 as wild group and 9 people carried ALDH2*1/*2 as mutation group. The good linear range of alcohol and acetaldehyde were 0-1 570.7 microg/mL and 0-5.1772 microg/mL, respectively. The AUC values of alcohol and acetaldehyde and the t1/2Z value of alcohol were higher in the mutation group than that in the wild group. But the CL/F value of alcohol was lower in the mutation group than that in the wild group (P<0.05). CONCLUSION After the consumption of alcohol, alcohol and acetaldehyde metabolism in blood slow down in ALDH2*1/*2 mutation group influenced by the inhibition of enzyme activity, leading to the accumulation of acetaldehyde in peripheral blood, thus reinforcing their effects in the body.
Alcohol Drinking ; Aldehyde Dehydrogenase/genetics* ; Aldehyde Dehydrogenase, Mitochondrial ; Ethanol/metabolism* ; Genotype ; Humans ; Polymerase Chain Reaction ; Polymorphism, Genetic

Bacillus sp. TSH1 is a butanol-producing microorganism newly isolated in our laboratory; it can grow and ferment under facultative anaerobic conditions, while sharing similar fermentation pathways and products with Clostridium acetobutylicum. To illustrate the relationships between the products and the enzyme activities in Bacillus sp. TSH1, key butanol- and ethanol-forming enzymes were studied, including butyraldehyde dehydrogenase, butanol dehydrogenase and alcohol dehydrogenase. The activities of the three enzymes increased rapidly after the initiation of fermentation. Activities of three enzymes peaked before 21 h, and simultaneously, product concentrations also began to increase gradually. The maximum activity of alcohol dehydrogenase was 0.054 U/mg at 12 h, butyraldehyde dehydrogenase 0.035 U/mg at 21 h and butanol dehydrogenase 0.055 U/mg at 15 h. The enzyme activities then decreased, but remained constant at a low level after 24 h, while the concentrations of butanol, acetone, and ethanol continued increasing until the end of the fermentation. The results will attribute to the understanding of the butanol metabolic mechanism, and provide a reference for further study of a facultative Bacillus metabolic pathway.
Alcohol Dehydrogenase ; metabolism ; Alcohol Oxidoreductases ; metabolism ; Aldehyde Oxidoreductases ; metabolism ; Anaerobiosis ; Bacillus ; classification ; genetics ; metabolism ; Butanols ; metabolism ; Fermentation ; Metabolic Networks and Pathways

BACKGROUNDThe most critical mechanism governing drug resistance in Candida albicans (C. albicans) involves efflux pumps, the functionality of which largely depends on energy metabolism. Alcohol dehydrogenase I (ADH1) plays an important role in intracellular energy metabolism. The aim of this study was to explore the relationship between ADH1 and drug resistance in C. albicans.

METHODSTwenty clinical C. albicans samples isolated from individual patients diagnosed with vulvovaginal candidiasis, and two C. albicans strains obtained from a single parental source (the fuconazole (FLC)-sensitive strain CA-1S and the FLC-resistant strain CA-16(R)) were included in our study. In accordance with the Clinical and Laboratory Standards Institute (CLSI) M27-A3 guidelines, we used the microdilution method to examine the FLC minimum inhibitory concentrations (MICs) and real-time reverse transcription polymerase chain reaction (RT-PCR) to measure the mRNA expression levels of ADH1 and the azole resistance genes CDR1, CDR2, MDR1, FLU1 and ERG11 in all the isolates.

RESULTSA highly significant positive correlation between the mRNA levels of ADH1 and the MICs (rs = 0.921, P = 0.000), as well as positive correlations between the mRNA level of ADH1 and those of CDR1, CDR2 and FLU1 (rs of 0.704, 0.772 and 0.779, respectively, P < 0.01), were observed in the 20 clinical C. albicans samples. The relative expression of ADH1 was upregulated 10.63- to 17.61-fold in all of the drug-resistant isolates. No correlations were found between the mRNA levels of ADH1 and those of MDR1 or ERG11 (P > 0.05). The mRNA levels of the examined drug resistance genes were higher in the CA-16(R) strain than in CA-1(S), and the mRNA levels of ADH1 in CA-16(R) were 11.64-fold higher than those in CA-1(S) (P < 0.05).

CONCLUSIONSThese results suggest that high levels of ADH1 transcription are implicated in FLC resistance in C. albicans and that the mRNA expression levels of ADH1 are positively correlated with those of CDR1, CDR2 and FLU1.

ATP-Binding Cassette Transporters ; genetics ; Alcohol Dehydrogenase ; genetics ; Candida albicans ; drug effects ; Candidiasis, Vulvovaginal ; microbiology ; Drug Resistance, Fungal ; genetics ; Drug Resistance, Multiple ; genetics ; Female ; Fluconazole ; pharmacology ; Fungal Proteins ; genetics ; Humans ; Membrane Transport Proteins ; genetics ; RNA, Messenger ; analysis

OBJECTIVETo investigate the correlation of G487A polymorphism of aldehyde dehydrogenase-2 (ALDH2) gene with hypertension in patients with coronary heart disease complicated by type 2 diabetes.

METHODSThis study was conducted among 167 patients with coronary heart disease complicated by diabetes mellitus. The polymorphisms of gene G487A ALDH2 were determined using polymerase chain reaction-restricted fragments length polymorphism technique (PCR-RFLP). According to the genotypes, the patients were divided into GG group (n=105) and GA/AA group (n=62), and the incidence of hypertension, risk factors of hypertension, systolic and diastolic pressures, and pulse pressure indexes were compared between the two groups. Multivariate logistic regression analysis was performed to adjust the effects of the confounding factors.

RESULTSThe incidence of hypertension in GA/AA group was significantly higher than that in GG group (P<0.05), and the former group showed a significantly greater differences between systolic and pulse pressure; the diastolic pressure was comparable between the two groups. Multivariate logistic regression analysis showed that GA/AA was associated with an increased risk of hypertension in synergy with high insulin level and insulin resistance.

CONCLUSIONALDH2 gene G487A polymorphism may be associated with hypertension in patients with coronary heart disease complicated by type 2 diabetes, and the patients with an A allele have a greater risk of developing hypertension.

Aged ; Alcohol Dehydrogenase ; genetics ; Coronary Disease ; complications ; genetics ; Diabetes Mellitus, Type 2 ; complications ; genetics ; Female ; Humans ; Hypertension ; etiology ; Male ; Middle Aged ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; Risk Factors

OBJECTIVETo examine the expression of cytochrome P450 related genes in oral submucous fibrosis tissue and to investigate the possible role of the genes in pathogenesis of oral submucous fibrosis (OSF).

METHODSBuccul mucosa tissues were obtained from OSF patients in early, medium and advanced stages, with each stage including 10 patients. Normal buccul mucosa tissues were collected from 10 patients undergoing oral and maxillofacial surgery as control. Oral submucous fibrosis-related genes were analysed by cDNA chips, and the results were submitted to the gene network database. Differentially expressed genes related to the pathway of CYP metabolism were indentifyed by the database analysis. Reverse transcription-polymerase chain reaction (RT-PCR) was used to verify the results from cDNA chips by increasing sample volume.

RESULTSThere were eight genes [CYP2B6, CYP2C18, CYP2F1, CYP3A5, microsomal glutathione S-transferase 2 (MGST2), alcohol dehydrogenase (ADH), UDP glucuronosyl transferase 2B15 (UGT2B15), ADH1C] which were related to the pathway of CYP metabolism. These genes were low expressed in all stages of OSF (P < 0.001).There were no differences in genes expression among the three stages of OSF (P > 0.05).

CONCLUSIONSThere were down-regulated genes related to the pathway of CYP metabolism in oral submucous fibrosis tissue. The ability of the pathway of CYP to metabolize and clear betel nut ingredients was reduced in OSF patients, which may play a role in the pathogenesis of OSF.

Adult ; Alcohol Dehydrogenase ; genetics ; metabolism ; Aryl Hydrocarbon Hydroxylases ; genetics ; metabolism ; Cytochrome P-450 CYP2B6 ; Cytochrome P-450 CYP3A ; genetics ; metabolism ; Cytochrome P-450 Enzyme System ; genetics ; metabolism ; Cytochrome P450 Family 2 ; Down-Regulation ; Glucuronosyltransferase ; genetics ; metabolism ; Glutathione Transferase ; genetics ; metabolism ; Humans ; Male ; Oligonucleotide Array Sequence Analysis ; Oral Submucous Fibrosis ; metabolism ; pathology ; RNA, Messenger ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Young Adult

OBJECTIVETo investigate the association of the polymorphisms of aldehyde dehydrogenase-2(ALDH2) and CYP2E1-RsaI genes and alcohol consumption with oral squamous cell carcinoma (OSCC).

METHODSThe genetic polymorphisms of ALDH2 and CYP2E1-RsaI were determined by polymorphism-polymerase chain reaction (PCR) technique in the peripheral blood leukocytes of 320 OSCC patients and 320 non-cancer controls.

RESULTSThe frequencies of ALDH2 variant genotypes and CYP2E1-RsaI (c2/c2) were 70.94% and 39.06% in the OSCC group and 43.44% and 20.62% in the control group (both P<0.01). The risk of OSCC with ALDH2 variant genotypes was significantly higher than that in control group (OR=3.178, 95% CI=1.917-4.749), whereas the subjects carried with CYP2E1-RsaI (c2/c2) also had a high risk of OSCC (OR=2.467, 95%CI=1.783-4.045). Combined analysis of the polymorphisms showed that percentage of ALDH2 variant genotypes/CYP2E1-RsaI (c2/c2) in OSCC group and control group was 32.19% and 6.25%, respectively (P<0.01). Carriers of ALDH2 variant genotypes/CYP2E1-RsaI (c2/c2) had a high risk of OSCC (OR=9.792, 95%CI=3.583-12.472). The percentage of alcohol consumption was significantly higher in OSCC group than in the control group (OR=2.861, 95% CI=1.541-4.781, P<0.01), and ALDH2 variant genotypes and CYP2E1-RsaI (c2/c2) showed synergic effects with alcohol consumption for the increased risk of OSCC (OR=41.152, 95%CI=19.903-67.551).

CONCLUSIONThe polymorphisms of ALDH2 and CYP2E1-RsaI genes and alcohol consumption, independently and synergically, increase the risk of OSCC.

Alcohol Drinking ; adverse effects ; Aldehyde Dehydrogenase ; Aldehyde Dehydrogenase, Mitochondrial ; Carcinoma, Squamous Cell ; etiology ; genetics ; Cytochrome P-450 CYP2E1 ; genetics ; Female ; Humans ; Male ; Middle Aged ; Mouth Neoplasms ; etiology ; genetics ; Polymorphism, Genetic ; Risk Factors

In order to successfully express the carbonyl reductase gene mldh in Bacillus subtilis and complete coenzyme regeneration by B. subtilis glucose dehydrogenase, the promoter PrpsD and the terminator TrpsD from B. subtilis rpsD gene were used as the expression cassette to be a recombinant plasmid pHY300plk-PrpsD-TrpsD. After that, the carbonyl reductase gene mldh was inserted into the previous plasmid and a plasmid pHY300plk-PrpsD-mldh-TrpsD was achieved, followed by transformed into B. subtilis Wb600 to obtain a recombinant B. subtilis Wb600 (pHY300plk-PrpsD-mldh-TrpsD). Subsequently, the results for whole-cell biotransformation from recombinant B. subtilis showed that it could be used to catalyze MAK (1-phenyl- 1-keto-2-methylaminopropane) to d-pseudoephedrine in the presence of glucose. The yield of d-pseudoephedrine could be up to 97.5 mg/L and the conversion rate of MAK was 24.1%. This study indicates the possibility of biotransformation production of d-pseudoephedrine from recombinant B. subtilis.
Alcohol Oxidoreductases ; genetics ; Bacillus subtilis ; genetics ; metabolism ; Glucose 1-Dehydrogenase ; chemistry ; metabolism ; Mutagenesis, Insertional ; Pseudoephedrine ; metabolism ; Recombinant Proteins ; biosynthesis ; genetics ; Recombination, Genetic