Alcohol drinking, mean corpuscular volume of erythrocytes, and alcohol metabolic genotypes in drunk drivers

Regular and irregular abuse of alcohol are global health priorities associated with diseases at multiple sites, including cancer. Mechanisms of diseases induced by alcohol are closely related to its metabolism. Among conventional markers of alcohol abuse, the mean corpuscular volume (MCV) of erythrocytes is prognostic of alcohol-related cancer and its predictivity increases when combined with functional polymorphisms of alcohol dehydrogenase (ADH1B [rs1229984] and ADH1C [rs698]) and the mitochondrial aldehyde dehydrogenase (ALDH2 [rs671]). Whether these genetic variants can influence abuse in alcohol drinking and MCV has never been examined in drunk-driving traffic offenders. We examined 149 drunk drivers, diagnosed as alcohol abusers according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth edition Text Revision (DSM-IV-TR) and enrolled in a probation program, and 257 social drinkers (controls), all Caucasian males. Alcohol intake was assessed according to self-reported drink-units/d and MCV unadjusted and adjusted for age, smoking, and body mass index. Multivariable models were used to compute MCV adjusted means. Genotype analyses were performed by PCR on DNA from blood. The adjusted MCV mean was higher in drunk-driving abusers than in controls (92 vs. 91 fL; P < .0001) and increased with the number of drink-units/d in both abusers and controls (P-trend = .0316 and .0089) already at intermediate quantities (0-1 vs. 2-4 drink-units/d: P = .054 and .024). Carriers of the common ADH1B*1/*1 (rs1229984) genotype were more likely to be drunk-driving abusers (P = .008), reported higher drink-units/d (P = .0126), and had larger MCV (P = .035). The rs698 ADH1C and rs671 ALDH2 polymorphisms were not associated with MCV. ADH1B*1/*1 polymorphism is significantly associated with being a drunk-driving abuser, higher alcohol drinking, and MCV enlargement. This suggests that drunk drivers with augmented MCV modulated by the alcohol metabolic ADH1B*1/*1 genotype may be at higher risk of driving incapability and of alcohol-related cancer.     

Alcohol consumption, alcohol dehydrogenase 1C (ADH1C) genotype, and risk of colorectal cancer in the Netherlands Cohort Study on diet and cancer

Within the Netherlands Cohort Study (1986), we examined associations between alcohol consumption, the alcohol dehydrogenase 1C (ADH1C) genotype, and risk of colorectal cancer (CRC). After a follow-up period of 7.3 years, 594 CRC cases with information on genotype and baseline alcohol intake were available for analyses. Adjusted incidence rate ratios (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. In subjects who reported to have consumed equal amounts of total alcohol both 5 years before baseline and at baseline, drinkers of ≥30 g of alcohol per day with the ADH1C*2/*2 genotype were associated—although not statistically significant—with an increased risk of CRC relative to abstainers with the ADH1C*1/*1 genotype (RR: 1.91, 95% CI: 0.68, 5.34). The risk estimate in this exposure group increased slightly when compared with light drinkers of ≥0.5-<5 g/day with the ADH1C*1/*1 genotype (RR: 2.32, 95% CI: 0.80, 6.72). The interaction term however, was not statistically significant (P > .05). In subjects who reported to have consumed equal amounts of total alcohol both 5 years before baseline and at baseline, drinkers of ≥30 g of alcohol per day were associated—although not statistically significant—with an increased risk of CRC relative to abstainers (RR: 1.38, 95% CI: 0.80, 2.38). This risk estimate for high-level drinkers became stronger when compared with light drinkers (RR: 1.74, 95% CI: 1.01, 2.99). As main effect of genotype, we observed that the ADH1C*2/*2 genotype was associated with a 42% increase in risk of CRC when compared with the ADH1C*1/*1 genotype. In conclusion, both genotype and alcohol consumption were associated with an increased risk of CRC. Owing to limited statistical power, we found no apparent evidence for the ADH1C genotype as effect modifier of the relationship between alcohol intake and CRC. Nevertheless, the interaction deserves further investigation in larger genetic epidemiologic studies.     

Distribution of ADH1B, ALDH2, CYP2E1∗6, and CYP2E1∗7B genotypes in Turkish population

The most well-known metabolic pathways from ethanol to acetaldehyde include alcohol dehydrogenase (ADH) and the microsomal ethanol oxidizing system that involves cytochrome P450 2E1 (CYP2E1). Acetaldehyde is further oxidized to acetate by aldehyde dehydrogenase (ALDH). The genetic variation of ADH1B, ALDH2, and CYP2E1 is different among racial populations and cause difference in elimination rates of alcohol. The aim of this study was to determine the polymorphisms of ADH1B (rs1229984; Arg47His), ALDH2 (rs671; Glu487Lys), CYP2E1*6 (rs6413432; T7632A), and CYP2E1*7B (rs6413420; G-71T) in unrelated healthy Turkish population and compare it with other populations. ADH1B and ALDH2 polymorphisms were analyzed with an allele-specific polymerase chain reaction (PCR) assay, and CYP2E1*6 and CYP2E1*7B polymorphisms were genotyped by PCR-restriction fragment length polymorphism method. ADH1B polymorphism analysis yielded the genotype distribution as 83.9% ADH1B*1/1 and 16.1% ADH1B*1/2, and no individuals with ALDH2*1/2 and ALDH2*2/2 genotypes were found in Turkish population. The genotype frequencies for CYP2E1*6 polymorphism were found as 85.3% for homozygote common, 14.1% for heterozygote, and 0.6% for homozygote uncommon. For CYP2E1*7B polymorphism, the genotype frequencies were determined to be 86.5% G/G, 13.5% for G/T; however, no individuals with homozygote uncommon genotype were detected. According to our study results, the genotype distributions of ADH1B, ALDH2, CYP2E1*6, and CYP2E1*7B in Turkish population were similar compared with Caucasian and some European populations, whereas differed significantly from East Asian populations. This study may be useful in epidemiological studies of the influence of ADH1B, ALDH2, CYP2E1*6, and CYP2E1*7B polymorphisms on diseases, including several types of cancer related to alcohol consumption and alcohol dependence.     

A comparison of Val81Met and other polymorphisms of alcohol metabolising genes in patients and controls in Northern Spain

The aim of this paper is to study polymorphism in the TH, ADH1B, ADH1C, ALDH2 and CYP2E1 genes so as to ascertain whether it is associated with excessive consumption of alcohol. The SNPs rs6356 of TH, rs1229984, rs2066702 of ADH1B; rs698, rs1693482 of ADH1C; rs671 of ALDH2; rs72559710, rs55897648, rs6413419, rs3813867, rs2031920, rs6413432 of CYP2E1 were studied in a sample of 172 high-level patients and 150 fully non-drinkers controls. Genotyping was performed using Rt-PCR with Taqman probes. SNPs located at ALDH2 and CYP2E1 showed no heterozygosity. Frequency distribution showed significant differences between the two groups studied for loci TH and ADH1B. The genotype Val/Val of TH locus increased in risk 1.988 times (95% CI: 1.006–3.930) that the subjects carrying the genotype Met/Met; and the genotype ADH1B*1/*1 of ADH1B locus increased in risk 3.811 times (CI: 1.660–8.749) that the subjects carrying the genotype ADH1B*1/*2. Alleles Val and ADH1B*1 may therefore increase the risk of the onset and development of this illness.     

Regulation of Alcohol and Acetaldehyde Metabolism by a Mixture of Lactobacillus and Bifidobacterium Species in Human

Excessive alcohol consumption is one of the most significant causes of morbidity and mortality worldwide. Alcohol is oxidized to toxic and carcinogenic acetaldehyde by alcohol dehydrogenase (ADH) and further oxidized to a non-toxic acetate by aldehyde dehydrogenase (ALDH). There are two major ALDH isoforms, cytosolic and mitochondrial, encoded by ALDH1 and ALDH2 genes, respectively. The ALDH2 polymorphism is associated with flushing response to alcohol use. Emerging evidence shows that Lactobacillus and Bifidobacterium species encode alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) mediate alcohol and acetaldehyde metabolism, respectively. A randomized, double-blind, placebo-controlled crossover clinical trial was designed to study the effects of Lactobacillus and Bifidobacterium probiotic mixture in humans and assessed their effects on alcohol and acetaldehyde metabolism. Here, twenty-seven wild types (ALDH2*1/*1) and the same number of heterozygotes (ALDH2*2/*1) were recruited for the study. The enrolled participants were randomly divided into either the probiotic (Duolac ProAP4) or the placebo group. Each group received a probiotic or placebo capsule for 15 days with subsequent crossover. Primary outcomes were measurement of alcohol and acetaldehyde in the blood after the alcohol intake. Blood levels of alcohol and acetaldehyde were significantly downregulated by probiotic supplementation in subjects with ALDH2*2/*1 genotype, but not in those with ALDH2*1/*1 genotype. However, there were no marked improvements in hangover score parameters between test and placebo groups. No clinically significant changes were observed in safety parameters. These results suggest that Duolac ProAP4 has a potential to downregulate the alcohol and acetaldehyde concentrations, and their effects depend on the presence or absence of polymorphism on the ALDH2 gene.     

Inhibition of human alcohol and aldehyde dehydrogenases by acetaminophen: Assessment of the effects on first-pass metabolism of ethanol

Acetaminophen is one of the most widely used over-the-counter analgesic, antipyretic medications. Use of acetaminophen and alcohol are commonly associated. Previous studies showed that acetaminophen might affect bioavailability of ethanol by inhibiting gastric alcohol dehydrogenase (ADH). However, potential inhibitions by acetaminophen of first-pass metabolism (FPM) of ethanol, catalyzed by the human ADH family and by relevant aldehyde dehydrogenase (ALDH) isozymes, remain undefined. ADH and ALDH both exhibit racially distinct allozymes and tissue-specific distribution of isozymes, and are principal enzymes responsible for ethanol metabolism in humans. In this study, we investigated acetaminophen inhibition of ethanol oxidation with recombinant human ADH1A, ADH1B1, ADH1B2, ADH1B3, ADH1C1, ADH1C2, ADH2, and ADH4, and inhibition of acetaldehyde oxidation with recombinant human ALDH1A1 and ALDH2. The investigations were done at near physiological pH 7.5 and with a cytoplasmic coenzyme concentration of 0.5 mm NAD⁺. Acetaminophen acted as a noncompetitive inhibitor for ADH enzymes, with the slope inhibition constants (K_is) ranging from 0.90 mm (ADH2) to 20 mm (ADH1A), and the intercept inhibition constants (K_ii) ranging from 1.4 mm (ADH1C allozymes) to 19 mm (ADH1A). Acetaminophen exhibited noncompetitive inhibition for ALDH2 (K_is = 3.0 mm and K_ii = 2.2 mm), but competitive inhibition for ALDH1A1 (K_is = 0.96 mm). The metabolic interactions between acetaminophen and ethanol/acetaldehyde were assessed by computer simulation using inhibition equations and the determined kinetic constants. At therapeutic to subtoxic plasma levels of acetaminophen (i.e., 0.2–0.5 mm) and physiologically relevant concentrations of ethanol (10 mm) and acetaldehyde (10 μm) in target tissues, acetaminophen could inhibit ADH1C allozymes (12–26%) and ADH2 (14–28%) in the liver and small intestine, ADH4 (15–31%) in the stomach, and ALDH1A1 (16–33%) and ALDH2 (8.3–19%) in all 3 tissues. The results suggest that inhibition by acetaminophen of hepatic and gastrointestinal FPM of ethanol through ADH and ALDH pathways might become significant at higher, subtoxic levels of acetaminophen.     

Effect of chronic alcohol consumption on the ethanol- and acetaldehyde-metabolizing systems in the rat gastrointestinal tract

The activities of alcohol dehydrogenase (ADH), catalase, microsomal ethanol-oxidizing system (MEOS) and aldehyde dehydrogenase (ALDH) were measured in gastric, small intestinal, colonic and rectal mucosal samples of rats fed on a liquid alcohol diet for 1 month. In the rectum and large intestine of control animals, the activities of ADH, MEOS and catalase were maximal, whereas the activity of ALDH was minimal. After chronic alcohol intoxication, MEOS activity increased significantly in the stomach. An activation of catalase and MEOS and a decrease of the low-K(M) ALDH activity were observed in the rectum of experimental animals. In rats consuming the alcohol diet, hypertrophy of crypts and an increased number of mitoses were noticed in colonic and rectal mucosa. Acute alcohol intoxication (2 g/kg, intragastrically) produced significantly higher acetaldehyde concentrations in the contents of the large intestine and rectum of rats receiving alcohol chronically compared to controls. Thus, after chronic alcohol intoxication, the large intestine regions showed a greater imbalance between the activities of acetaldehyde-producing and -oxidizing enzymes, which resulted in accumulation of acetaldehyde. This mechanism can account for the local toxicity of ethanol after its chronic consumption, and relates the development of mucosal damage and compensatory hyper-regenerative processes, and possibly carcinogenesis, in the colonic and rectal mucosae of alcoholics to the effects of acetaldehyde.     

Relationships of alcohol dehydrogenase 1B (<Emphasis Type="Italic">ADH1B</Emphasis>) and aldehyde dehydrogenase 2 (<Emphasis Type="Italic">ALDH2</Emphasis>) genotypes with alcohol sensitivity,drinking behavior and problem drinking in Japanese older men

Objectives

Many East Asians have the genetic polymorphisms rs1229984 in alcohol dehydrogenase 1B (ADH1B) and rs671 in aldehyde dehydrogenase 2 (ALDH2). Here we analyzed the relationships of the two genotypes with alcohol sensitivity, drinking behavior and problem drinking among older and younger men living in rural areas of Japan.

Methods

The subjects were 718 Japanese men aged 63.3 ± 10.8 (mean ± SD), categorized into the older (≥65 years, n = 357) and younger (<65 years, n = 361) groups. Facial flushing frequency, drinking behavior and positive CAGE results were compared among the genotypes using Bonferroni-corrected χ² test and a multivariate logistic regression analysis adjusting for age, BMI and lifestyle factors.

Results

The frequency of ‘always’ facial flushing among the ADH1B*1/*2 carriers was significantly lower than that among the ADH1B*2/*2 carriers in the older group (P < 0.01). The alcohol consumption (unit/day) in the ADH1B*1/*2 carriers tended to be higher compared with that in the ADH1B*2/*2 carriers among the older group (P = 0.050). In the younger group, no significant differences in alcohol sensitivity and drinking habits were generally found among the ADH1B genotypes. The ADH1B*1/*1 genotype tended to be positively associated with problem drinking in the older group (P = 0.080) but not in the younger group. The ALDH2 genotypes consistently and strongly affected the alcohol sensitivity, drinking behavior and problem drinking in both the younger and older group.

Conclusions

We for the first time observed a significant difference in alcohol sensitivity between ADH1B*1/*2 and ADH1B*2/*2 in older men aged 65 and above.

     

Roles of defective <Emphasis Type="Italic">ALDH2</Emphasis> polymorphism on liver protection and cancer development

Because serum transaminases elevate alcohol dose dependently as a consequence of liver injury, they serve as useful biological markers of excessive drinking. However, these markers are inadequate in individuals with a defective allele of the aldehyde dehydrogenase 2 gene, ALDH2*2, because they show a different correlation with the amount of ethanol. For example, the serum alanine aminotransferase (ALT) level could become even lower than the baseline after alcohol intake in ALDH2*2 carriers. In fact, multiple studies suggest that ALDH2*2 is a hepato-protective factor in healthy individuals. Importantly, excessive drinking is particularly dangerous in carriers of ALDH2*2 because the risk of alcohol-related cancer is much higher than that for ALDH2*1/*1 carriers. Without recognizing the genotype interaction on serum transaminase, the opportunity to warn people about potential cancer risks is missed owing to incorrect interpretation. This is particularly important in East Asian countries where approximately half of the population carries the ALDH2*2 allele. To date, the mechanism of liver protection from ethanol load in individuals with ALDH2*2 has not been fully elucidated. However, some reasonable mechanisms have been suggested by experimental studies, including remodelling of detoxifying systems. Further studies to uncover the whole mechanism are anticipated.     

Correlation between total phenolic and mineral contents with antioxidant activity of eight Malaysian bananas (Musa sp.)

Correlations between total phenolic and mineral contents with antioxidant activities of pulps and peels from eight banana (Musa sp.) cultivars were studied. The total phenolic contents were determined using Folin-Ciocalteu colorimetric method, and antioxidant activities were measured using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and ferric reducing antioxidant potential (FRAP) assay. The highest total phenolic content (76.37 ± 1.79 mg GAE/g d.w.) was obtained from the freeze-dried extract of fresh pulps of Raja cultivar. The maximum activity of DPPH (19.39 ± 0.15 mg TE/g d.w.) was recorded for the chloroform extract of dried peels of Mas cultivar. Meanwhile, the highest activity of FRAP was shown by most of the chloroform extracts of dried pulps, dominated by Awak cultivar (22.57 ± 0.13 mg TE/g d.w.). With few exceptions, peel extracts exhibited higher total phenolic content and stronger antioxidant activities than that of the pulps. Very weak correlation between total phenolic content and FRAP activity was observed, yet it is higher (r² = 0.1614, p < 0.0001) than that of total phenolic content and DPPH activity (r² = 0.02339, p < 0.05). A moderate correlation between DPPH and FRAP activities was obtained (r² = 0.3533, p < 0.0001). For mineral analysis, potassium (K) is the major element found in both fresh pulps and peels followed by P, Mg and Na. Fresh peels of Raja consisted the highest amount of K (1387.5 mg/100 g f.w.). With exception of Mn, no correlation was found between mineral content and antioxidant activity. A moderate correlation between Mn content and DPPH activity was observed (r² = 0.2855, p < 0.0001).     

Pooled analysis of alcohol dehydrogenase genotypes and head and neck cancer: a HuGE review

Possession of the fast metabolizing alleles for alcohol dehydrogenase (ADH), ADH1B*2 and ADH1C*1, and the null allele for aldehyde dehydrogenase (ALDH), ALDH2*2, results in increased acetylaldehyde levels and is hypothesized to increase the risk of head and neck cancer. To examine this association, the authors undertook a Human Genome Epidemiology review on these three genes and a pooled analysis of published studies on ADH1C. The majority of Asians had the fast ADH1B*2 and ADH1C*1 alleles, while the majority of Caucasians had the slow ADH1B*1/1 and ADH1C*1/2 genotypes. The ALDH2*2 null allele was frequently observed among Asians, though it was rarely observed in other populations. In a pooled analysis of data from seven case-control studies with a total of 1,325 cases and 1,760 controls, an increased risk of head and neck cancer was not observed for the ADH1C*1/2 genotype (odds ratio = 1.00, 95% confidence interval: 0.81, 1.23) or the ADH1C*1/1 genotype (odds ratio = 1.14, 95% confidence interval: 0.92, 1.41). Increased relative risks of head and neck cancer were reported for the ADH1B*1/1 and ALDH2*1/2 genotypes in several studies. Recommendations for future studies include larger sample sizes and incorporation of relevant ADH and ALDH genes simultaneously, as well as other genes. These considerations suggest the potential for the organization of a consortium of investigators conducting studies in this field.     

Replication of rubella vaccine population genetic studies: Validation of HLA genotype and humoral response associations

Purported genetic associations found in population studies require validation for confirmation. We previously reported rubella vaccine-induced immune responses and HLA associations in 346 adolescents, age 12–18 years (1st cohort), following two doses of a rubella-containing vaccine. We sought to replicate the associations discovered in that work by verifying these associations in a new cohort of 396 subjects, age 11–19 years (2nd cohort), all having had two doses of a rubella-containing vaccine. We found that B*2705 (median 1st cohort 20.9 IU/ml, p = 0.028; 2nd cohort 20.5 IU/ml, p = 0.001) and DPA1*0201 (median 1st cohort 32.5 IU/ml, p = 0.048; 2nd cohort 25.8 IU/ml, p = 0.025) alleles were consistently associated with lower rubella-induced antibodies. Further, DPB1*0401 (median 1st cohort 43.5 IU/ml, p = 0.021; 2nd cohort 36.2 IU/ml, p = 0.002) alleles were associated with higher antibody levels in both populations. The association of DRB1*04-DQB1*03-DPB1*03 (mean 1st cohort 25.2 IU/ml, p = 0.011; 2nd cohort 21.4 IU/ml, p = 0.032) and DRB1*15/16-DQB1*06-DPB1*03 (1st cohort 16.3 IU/ml, p = 0.043; 2nd cohort 19.1 IU/ml, p = 0.023) haplotypes with lower rubella-specific antibodies was observed in both studies. This study provides confirmatory evidence for an association between specific class I and II HLA markers and haplotypes with rubella vaccine-induced humoral responses and lends further weight to their influence on rubella immune responses.     

青海藏族人群ADH3、ALDH2基因多态性及其与饮酒行为的关系

目的 了解青海藏族男性乙醇脱氢酶3(ADH3)和乙醛脱氢酶2(ALDH2)基因多态性分布及其与饮酒行为的关系.方法 采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法对ADH3和ALDH2基因型进行检测;采用回顾性问卷调查研究对象的饮酒行为.结果 等位基因ADH3*2和ALDH2*2在藏族人群中的比例分别为7.79％和22.21％;不饮酒组中等位基因ALDH2*2、ADH3*1频率高于饮酒者;危险饮酒组中等位基因ALDH2*2、ADH3*1频率低于安全饮酒者.结论 ADH3、ALDH2基因与青海藏族男性人群饮酒行为有关.     

Comparison of carotenoid and anthocyanin profiles of raw and boiled Solanum tuberosum and Solanum phureja tubers

Tubers of the closely related species Solanum tuberosum (potatoes) and Solanum phureja belong to the staff of life for humans. The coloration of the often very colorful tubers is caused by carotenoids (especially xanthophylls) and anthocyanins. The new S. phureja cultivars Mayan Gold and Mayan Twilight, the new S. tuberosum cultivar Red Laura and the traditional S. tuberosum variety Shetland Black were analyzed for their pigment content. The dominant anthocyanin in the red-skinned cultivars Red Laura and Mayan Twilight was characterized as pelargonidin-3-coumarylrutinoside-5-glucoside by LC-ESI-MS. The blue pigment of the Shetland Black cultivar was petunidin-3-coumaroylrutinoside-5-glucoside. Red Laura contained 10 mg anthocyanins g⁻¹ dry weight and Shetland Black 31 mg anthocyanins g⁻¹ dry weight. The main carotenoids in raw tubers are 9-cis-violaxanthin, lutein and one unidentified carotenoid in all S. tuberosum and S. phureja cultivars. Minor compounds were identified as neoxanthin and neochrome. Additionally, zeaxanthin and one further unidentified carotenoid could be found in Red Laura and Mayan Gold. No differences in the carotenoid composition between peel and parenchyma could be found. Total carotenoid content ranged from 2.57 ± 0.53 μg g⁻¹ dry weight in Shetland Black to 14.77 ± 2.22 μg g⁻¹ dry weight in Red Laura (calculated as β-carotene-equivalents). In heat processed tubers, high amounts of carotenoids either changed from all-trans to 9-cis and 13-cis-isomeric form or was degraded. The total pigment content was decreased by heat processing in all cultivars. 8.23 ± 2.98 μg g⁻¹ dry weight could be found in Mayan Twilight and 1.51 ± 0.31 μg carotenoids g⁻¹ dry weight in Shetland Black.     

醛、醇脱氢酶基因多态性与三氯乙烯药疹样皮炎易感性的关系

目的研究醛脱氢酶、醇脱氢酶基因多态性与三氯乙烯药疹样皮炎易感性的关系。方法应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法,比较108例三氯乙烯药疹样皮炎病人和145例健康三氯乙烯接触工人醛脱氢酶2(ALDH2)、醇脱氢酶2(ADH2)和醇脱氢酶3(ADH3)的基因多态性分布,并计算相对危险度(OR)。结果ADH2和ADH3基因型分布在病人与接触对照工人中无显著性差异;ALDH2变异型基因(ALDH2*1/*2+ALDH2*2/*2)频率在病人中显著低于接触对照工人(分别为27·8%和43·4%,P=0·011),使三氯乙烯药疹样皮炎的危险性显著降低(OR=0·50,95%CI=0·29~0·85)。结论高活性ALDH2可能是导致三氯乙烯药疹样皮炎个体易感性差异的原因之一。     

Antioxidants in digestive tracts and gonads of green urchin (Strongylocentrotus droebachiensis)

Digestive tracts and gonads of green urchin (Strongylocentrotus droebachiensis) were evaluated for their antioxidant potential and total phenol and flavonoid contents. Antioxidant potentials of freeze-dried samples were evaluated using lipophilic and hydrophilic oxygen radical absorbance capacity (ORAC) assays. Analyzed samples showed antioxidant activity with total ORAC values of 864 and 885 μmol of TE/g d.w. for digestive tracts and gonads, respectively. Acetonitrile-rich and ethyl acetate extracts from freeze-dried samples showed ORAC values (1500-2100 μmol of TE/g) higher than crude tissues (∼870 μmol of TE/g), while water-rich extracts were less active (260-370 μmol of TE/g). Eluates 1 and 2 obtained from C₁₈ solid-phase extraction of the water-rich fraction showed ORAC values (650-1600 μmol of TE/g) up to 6 times higher than their parent extracts. Total phenol and flavonoid contents of freeze-dried samples ranged from 53 to 123 mg of GAE/100 g d.w. and 1.4-1.8 mg of RE/100 g, respectively. ORAC values from digestive tracts samples showed significant correlations with total phenols (r² = 0.76, p = 0.049, n = 12) and flavonoids (r² = 0.80, p = 0.021, n = 12), while a very weak correlation was observed for samples from gonads. This is the first study to quantify antioxidant properties of green urchin tissues, and show that edible gonads might provide valuable antioxidants to consumers while digestive tracts might be valorized as an alternative source of antioxidants in food additive ingredients.     

Association of alcohol dehydrogenase 2 and aldehyde dehydrogenase 2 genotypes with fasting plasma glucose levels in Japanese male and female workers

AIMS: The objective was to clarify the effect of alcohol dehydrogenase 2 (ADH2) and aldehyde dehydrogenase 2 (ALDH2) genotypes on the diabetic risk in Japanese workers. METHODS: At the time of mandatory health checkup, the ADH2 and ALDH2 genotypes, as well as fasting plasma glucose (FPG) levels, body mass index (BMI), smoking habit, and weekly alcohol intake, were examined in 492 men and 183 women working at motor vehicle dealerships. RESULTS: In using two-way analysis of variance to manipulate ADH2 and ALDH2 genotypes and alcohol intake (>70 g/week for men and >35 g/week for women), the FPG level after the adjustment for age, BMI, smoking habit, and another genotype was significantly higher in the men with ADH2*1/1 genotype than in those with the other genotypes, but there was no significant difference in the FPG level between the men with and without ALDH2*1/1 genotype. In contrast, the women with ALDH2*1/1 genotype had significantly lower FPG levels than those with the other genotypes, but there was no significant difference in the FPG level between the women with and without ADH2*1/1 genotype. Also, a significant interaction between ethanol intake and ALDH2 genotypes was seen only in the women. CONCLUSIONS: These findings suggest that genotypes of ADH2 and ALDH2 can modify the diabetic risk, irrespective of amounts of alcohol consumed. Also, there may be sex differences in the effect of these enzyme genotypes on glucose metabolism.     

Overview of the role of alcohol dehydrogenase and aldehyde dehydrogenase and their variants in the genesis of alcohol-related pathology

Alcohol dehydrogenase (ADH) and mitochondrial aldehyde dehydrogenase (ALDH2) are responsible for metabolizing the bulk of ethanol consumed as part of the diet and their activities contribute to the rate of ethanol elimination from the blood. They are expressed at highest levels in liver, but at lower levels in many tissues. This pathway probably evolved as a detoxification mechanism for environmental alcohols. However, with the consumption of large amounts of ethanol, the oxidation of ethanol can become a major energy source and, particularly in the liver, interferes with the metabolism of other nutrients. Polymorphic variants of the genes for these enzymes encode enzymes with altered kinetic properties. The pathophysiological effects of these variants may be mediated by accumulation of acetaldehyde; high-activity ADH variants are predicted to increase the rate of acetaldehyde generation, while the low-activity ALDH2 variant is associated with an inability to metabolize this compound. The effects of acetaldehyde may be expressed either in the cells generating it, or by delivery of acetaldehyde to various tissues by the bloodstream or even saliva. Inheritance of the high-activity ADH beta2, encoded by the ADH2*2 gene, and the inactive ALDH2*2 gene product have been conclusively associated with reduced risk of alcoholism. This association is influenced by gene-environment interactions, such as religion and national origin. The variants have also been studied for association with alcoholic liver disease, cancer, fetal alcohol syndrome, CVD, gout, asthma and clearance of xenobiotics. The strongest correlations found to date have been those between the ALDH2*2 allele and cancers of the oro-pharynx and oesophagus. It will be important to replicate other interesting associations between these variants and other cancers and heart disease, and to determine the biochemical mechanisms underlying the associations.