Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increased alcohol consumption causes hypertension and leads to higher death rates by hemorrhagic strokes. About half of the Japanese population have inactive low Km aldehyde dehydrogenase (ALDH2), which metabolizes acetaldehyde to acetic acid at very low concentrations, leading to severe pharmacological effects of aldehyde when drinking alcohol. We determined persons with inactive ALDH2 using a ethanol patch test. All male workers (n + 163), aged from 21 to 62 years in one factory in Japan took part. They were divided into two groups by alcohol consumption (nondrinkers, light drinkers of < 32 ml/l ethanol per day and moderate to heavy drinkers of > or = 32 ml ethanol per day). The prevalence of persons with inactive ALDH2 was 52.1%. The prevalence of moderate to heavy drinkers among persons with inactive ALDH2 was significantly lower than that among those with active ALDH2 (23% and 41%, respectively: P < 0.05). No significant differences of BP were observed between ALDH2 inactive and active groups at the same consumption of alcohol. This study showed a significant relationship between categories of alcohol use and SBP and DBP (P < 0.05, respectively) controlled for age and body mass index. The mechanism by which alcohol use elevates BP is unlikely to be related to the inactive ALDH2. However, inactive ALDH2 may act as a protective factor against hypertension by reducing alcohol consumption.
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PMID:Low-Km aldehyde dehydrogenase deficiency does not influence the elevation of blood pressure by alcohol. 800 21

A case control study on male primary hepatocellular carcinoma(HCC) and hepatitis B or C virus and some potential risk factors, e.g. blood transfusion, aldehyde dehydrogenase 2(ALDH2) genotype and drinking habits, was performed using two controls, i.e. a hospital control(HC) and a community control(CC) in Fukuoka and Saga Prefectures. Cases were obtained from the Second Department of Internal Medicine, Kurume University Hospital. The HCs were obtained from inpatients of two general hospitals in Kurume and the CCs were randomly sampled from the Kurume citizens being matched with age and sex to each case. Based on the HCs, odds ratios(ORs) of developing male HCC were statistically significant due to HBsAg or anti-HCV antibody positive status. Some discrepancies were observed between the two controls, i.e. higher proportions of past histories of diabetes or hypertension, of ALDH2 typical homozygote(ALDH2(1)/ALDH2(1)), and of heavy drinkers among the HCs, suggesting slight deviation of the HCs from the CCs in alcohol related aspects. Although ORs regarding accumulated amount of alcohol intake by age 40 based on the HCs were insignificant, two of the three corresponding ORs based on the CCs were statistically significant. Judging from alcohol related aspects between the two controls, the ORs for alcohol based on the HCs seems to be underestimated.
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PMID:A case-control study on male hepatocellular carcinoma based on hospital and community controls. 957 88

The characteristics of alcohol-induced flushing response were studied in some Siberian Native populations (Chukchi, Eskimo, Jakuts, Udege, and Nanaian). Flushing peculiarities were estimated and the interrelationship with drinking patterns, the ethanol patch test (EPT), and somatic disorders were analyzed. Frequency of flushing response varied from 9.0% to 66.7%, and was more often apparent among females. Only the Nanaian demonstrated typical flushing, which did not allow them to consume high doses of alcohol. In the rest of the populations flushing was "atypical," i.e., appearing sometimes after high doses of alcohol but not interrupting alcohol drinking, and not associated with a positive EPT. Direct genotyping in DNA samples of Chukotka Natives did not reveal atypical allele aldehyde dehydrogenase (AIDH 2/2). Frequencies of alcohol problems, alcohol dependence symptoms, and somatic disorders (arterial hypertension, silent ischemia, diffuse liver lesions, and noncalculous cholecystitis) were higher among atypical flushers compared to nonflushers (p < 0.05-0.01). The mechanism of the observed atypical flushing response is unknown. We speculate on its hereditary nature, since flushing alcoholics, compared to nonflushers, reported that their parents had flushing responses significantly more often. Further studies are required.
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PMID:Flushing response and its role in alcohol disease in Siberian populations. 1009 24

Taurine is known to lower blood pressure in essential hypertension and some experimental hypertensive models. Taurine has also been reported to activate aldehyde dehydrogenase and to inhibit the elevation of plasma acetaldehyde concentration after ethanol intake. Because acetaldehyde, the first metabolite of ethanol, is suspected to be responsible for many adverse effects of alcohol consumption, we examined the effect of taurine supplementation on ethanol-induced hypertension and abnormalities in the intracellular cation metabolism in Witar-Kyoto rats. In Study 1, systolic blood pressure and intraplatelet free calcium were significantly higher in rats who received 15% ethanol in drinking water than in control rats. Oral taurine supplementation (1% taurine and 15% ethanol in drinking water) completely prevented the development of ethanol-induced hypertension. Intraerythrocyte sodium and intraplatelet free calcium were significantly decreased in taurine-supplemented rats as compared with rats who received 15% ethanol only. In Study 2, hemoglobin-associated acetaldehyde (HbAA) was measured as a marker of protein-bound acetaldehyde. HbAA was significantly elevated in rats who received 5% ethanol in drinking water as compared with control rats. Taurine supplementation (1% taurine and 5% ethanol in drinking water) significantly decreased HbAA. Our findings suggest that the oral supplementation of taurine prevents ethanol-induced hypertension by decreasing protein bound acetaldehyde and altering the cation handling by the membrane.
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PMID:Oral taurine supplementation prevents the development of ethanol-induced hypertension in rats. 1082 Nov 39

In Japanese and other Asians, the prevalence of genetically decreased mitochondrial aldehyde dehydrogenase (ALDH2) activity is higher than in Caucasians. The aim of this study was to elucidate the relation between ALDH2 genotypes and blood pressure levels or hypertension in Japanese. After obtaining informed consent for genetic analysis from 917 men and 1,478 women who lived in a mountainous farming region near Kyoto and who were free from cardiovascular disease and liver dysfunction, the authors identified the ALDH2 genotype in all subjects. Differences in blood pressure level among genotypes were then compared by analysis of covariance, and the relation between genotypes and hypertension was also analyzed by logistic regression analysis. The frequencies of genotypes *1/*1, *1/*2, and *2/*2 were 44.7%, 46.9% and 8.4% in men, and 50.1%, 43.2% and 6.8% in women, respectively. In men, systolic and diastolic blood pressures tended to decrease in the order of *1/*1>*1/*2>*2/*2. However, adjustment for confounding factors including alcohol consumption resulted in the disappearance of significance. Logistic regression analysis adjusted for the same confounding factors for men showed that the odds ratios (OR) of being hypertensive in the *2 allele to not having *2 allele were 0.67 (95% confidence interval (CI): 0.47-0.96). However, in the subgroup analyses, this relation was not observed in the group having a below-median level of alcohol consumption (OR = 0.92; 95% CI: 0.53-1.62) or in the group not taking antihypertensive agents (OR = 0.77; 95% CI: 0.52-1.15). Furthermore, we did not observe any relation between the ALDH2/*2 allele and hypertension in women (OR = 1.07; 95% CI: 0.80-1.42). The results suggest that there may be no causal relation between hypertension and the ALDH2 genotype per se, after excluding for some confounding factors, especially for alcohol drinking.
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PMID:Epidemiologic study of the association of low-Km mitochondrial acetaldehyde dehydrogenase genotypes with blood pressure level and the prevalence of hypertension in a general population. 1248 9

Recent studies indicate that some patients with nonalcoholic fatty liver have ongoing liver injury that may progress from steatosis to steatohepatitis or fibrosis. The present study was designed to clarify the clinical features of liver dysfunction observed in the course of workplace physical check-ups in relation to multiple risk factor syndrome including obesity, hyperlipidemia, hypertension, and impaired glucose tolerance, and to clarify the involvement of aldehyde dehydrogenase 2 (ALDH2) and beta(3)-adrenergic receptor (beta3-AR) gene polymorphisms in elevation of liver enzymes. One hundred forty-eight male workers 35 years of age were enrolled. They were requested to answer questionnaires about drinking and smoking habits, and underwent urinalysis, physical and peripheral blood examinations, blood chemistry, electrocardiogram and chest x-rays. The genotypes of ALDH2 and beta3-AR were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The subjects were divided into active ALDH2 or inactive ALDH2 groups. They were also divided into 2 groups according to the beta3-AR genotype. The relationships between ALDH2 and beta3-AR gene polymorphism and the results of the physical examination including liver function tests were analyzed. The subjects were also divided according to the number of components of metabolic syndrome. The prevalence of elevated alanine aminotransferase (ALT) level increased with the accumulation of components of metabolic syndrome. Active ALDH2 was associated with elevated ALT level to a greater degree than beta3-AR polymorphism. Among those with normal body mass index (BMI), the genotypes of ALDH2 and beta3-AR were strongly associated with elevated ALT level. Logistic regression analysis revealed that BMI, triglyceride level, and ALDH2 genotype were associated with ALT elevation. In conclusion, evaluating the genotype of ALDH2 and beta3-AR may assist in predicting and preventing the development of fatty liver which may be related to multiple risk factor syndrome.
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PMID:Aldehyde dehydrogenase 2 and beta3-adrenergic receptor gene polymorphisms: their association with elevated liver enzymes and metabolic syndrome. 1450 13

There is a genetic difference in sensitivity to alcohol in Orientals, which is known to be mainly due to polymorphisms of alcohol-metabolizing enzymes such as aldehyde dehydrogenase. Habitual alcohol drinking is a risk factor for hypertension. However, it has not been determined whether individual sensitivity to alcohol influences the relationship between alcohol consumption and blood pressure. In this study, the relationship between amount of alcohol consumption and blood pressure was compared between groups of subjects with low and high sensitivities of circulatory response to alcohol. Sensitivity to alcohol in subjects (306 male workers) was evaluated by a self-administered questionnaire on symptoms (skin flushing and palpitation) that appear when drinking alcohol. Weight, height and blood pressure were measured. In subjects with high sensitivity to alcohol, systolic blood pressure was significantly higher in the subgroup of moderate-to-heavy drinkers (30 g/day or more) than in the subgroups of non-drinkers and light drinkers (less than 30 g/day). On the other hand, in subjects with low sensitivity to alcohol, systolic blood pressure in the subgroup of non-drinkers was not significantly different from that in the subgroups of light drinkers and moderate-to-heavy drinkers. The amount of daily alcohol consumption was significantly correlated with both systolic and diastolic blood pressures in subjects with high sensitivity to alcohol but not in subjects with low sensitivity to alcohol. Pressor effects of alcohol drinking on blood pressure were significant only in subjects with high sensitivity to alcohol, suggesting that there is a greater risk of development of hypertension from drinking large amounts of alcohol in people with high sensitivity to alcohol.
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PMID:Sensitivity of circulatory response to alcohol influences the relationship between alcohol consumption and blood pressure in Orientals. 1612 58

We previously reported that the prevalence of elevated alanine aminotransferase (ALT) increases with accumulation of metabolic syndrome components, and a greater degree of involvement of aldehyde dehydrogenase 2 (ALDH2) than beta3-adrenergic receptor gene (beta3-AR) polymorphisms. The present study was designed to clarify the effect of aging, lifestyle and the two gene polymorphisms on the relationship between 4 components of the metabolic syndrome (obesity, hypertension, dyslipidemia and impaired glucose tolerance) and elevated ALT values in a subset of 73 out of 148 male workers who were 35 years of age in the baseline study and 40 years old in the present study. Study subjects completed questionnaires about drinking and smoking habits, and underwent urinalysis, physical examination and peripheral blood tests, blood chemistry, electrocardiogram and chest X-rays each year as required by Japanese law. Information from the questionnaires and physical examinations, including liver function tests, were compared with previously reported ALDH2 and beta3-AR genotypes for the 73 workers. Of the 73 workers studied, 14 (19%) demonstrated decrease in metabolic syndrome components, 39 (53%) demonstrated no change, and 20 (27%) demonstrated an increase. Ten workers (14%) showed liver dysfunction at age 35 and 20 workers (27%) at age 40. Fourteen workers were newly diagnosed as having liver dysfunction at their 40-year checkup, thus being associated with the BMI and an active ALDH2 genotype. Accumulation of components of the metabolic syndrome were associated with the presence of liver dysfunction at 35 years. In conclusion, these findings indicate that ALDH2 genotyping as well as lifestyle habits may be important factors in causing metabolic syndrome with liver dysfunction.
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PMID:Change of components of the metabolic syndrome in a workers' health checkup after five years--relation with elevated liver enzymes, gene polymorphisms for ALDH 2, beta3-AR and lifestyle. 1640 83

Low ethanol intake is known to have a beneficial effect on cardiovascular disease. In cardiovascular disease, insulin resistance leads to altered glucose and lipid metabolism resulting in an increased production of aldehydes, including methylglyoxal. Aldehydes react non-enzymatically with sulfhydryl and amino groups of proteins forming advanced glycation end products (AGEs), altering protein structure and function. These alterations cause endothelial dysfunction with increased cytosolic free calcium, peripheral vascular resistance, and blood pressure. AGEs produce atherogenic effects including oxidative stress, platelet adhesion, inflammation, smooth muscle cell proliferation and modification of lipoproteins. Low ethanol intake attenuates hypertension and atherosclerosis but the mechanism of this effect is not clear. Ethanol at low concentrations is metabolized by low Km alcohol dehydrogenase and aldehyde dehydrogenase, both reactions resulting in the production of reduced nicotinamide adenine dinucleotide (NADH). This creates a reductive environment, decreasing oxidative stress and secondary production of aldehydes through lipid peroxidation. NADH may also increase the tissue levels of the antioxidants cysteine and glutathione, which bind aldehydes and stimulate methylglyoxal catabolism. Low ethanol improves insulin resistance, increases high-density lipoprotein and stimulates activity of the antioxidant enzyme, paraoxonase. In conclusion, we suggest that chronic low ethanol intake confers its beneficial effect mainly through its ability to increase antioxidant capacity and lower AGEs.
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PMID:Beneficial effect of low ethanol intake on the cardiovascular system: possible biochemical mechanisms. 1732 32

The objective of the present study was to examine the association between a polymorphism of the aldehyde dehydrogenase 2 (ALDH2) gene and lacunar infarcts of the brain. We conducted a population-based, cross-sectional study on residents from two age groups (61- and 72-year olds). A total of 376 subjects participated in the study, which included brain magnetic resonance image and genetic analysis of the ALDH2 gene. Of the 61- and 72-year-old subjects, 46.4% and 64.3%, respectively, had one or more lacunar infarcts. The average number of infarcts also increased from 2.0 to 2.8 in men and from 2.3 to 3.5 in women. No significant association between the ALDH2 genotype and the presence of lacunar infarction (> or =1) was found. However, in subjects with lacunar infarction, the genotype of ALDH2 *1/*1 was associated with a larger number of the lesion ['single' versus 'multiple' odds ratio (OR) 3.73, 95%CI: 1.43-9.74] in men. The OR was comparable even after adjusting for alcohol consumption, tobacco habits, age, hypertension, hypercholesterolemia, and diabetes mellitus (DM) (OR 3.88; 95% CI: 1.10-13.66). In women, there was no significant association between the ALDH2 genotypes and lacunar infarcts. The present study revealed that the ALDH2 *1/*1 genotype was significantly associated with the prevalence of multiple lacunar infarcts in Japanese men.
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PMID:A polymorphism of the aldehyde dehydrogenase 2 gene is a risk factor for multiple lacunar infarcts in Japanese men: the Takahata Study. 1738 93


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