Alcohol dehydrogenase-2 and aldehyde dehydrogenase-2 genotypes and male alcohol use disorders in Khon Kaen,north-east Thailand

A case-control study on the relationship between alcohol dehydrogenase-2 (ADH2), aldehyde dehydrogenase-2 (ALDH2) and male probable alcohol use disorders (AUD) was performed in Khon Kaen, north-east Thailand. One hundred and fifty-three paired cases (probable AUD) and controls (non-probable AUD) were sampled from villagers aged 18-65 years using the modified Michigan Alcoholism Screening Test - Thai version, controls being matched for gender, age (+/- 4 years) and village. All of the cases and 86.9% of the controls were current drinkers. The percentage of ADH2*1/1 among cases was 47.1%, being significantly larger than the 29.4% among controls, and yielding a univariate odds ratio (OR) of 2.421* (95% confidence interval (CI) = 1.419-4.132) for developing probable AUD. The ALDH2*1/1 proportion among cases, 92.8%, was comparable to the 92.2% among controls, yielding a univariate OR of 1.100 (95%CI = 0.757-1.599). Multivariate analysis based on a conditional logistic regression model and a hierarchically well-formulated model strategy revealed that: (i) the OR of developing probable AUD due to 1 g increment of daily ethanol drinking was 1.110* among farmers (95%CI = 1.054-1.170); (ii) OR due to 1 g increment of daily ethanol drinking was 1.329* among non-farmers (95%CI = 1.109-1.593); (iii) OR due to either ADH2*1/1 or ALDH2*1/1 was insignificant; and (iv) the daily amount of smoking is independently associated with probable AUD. The present findings suggest that one of the genetic factors that may be related to probable AUD among Thai males living in the north-east is the ADH2 gene.     

Alcohol drinking frequency is more directly associated with alcohol use disorder than alcohol metabolizing enzymes among male Japanese

The development of alcohol use disorder (AUD) is related to various social, economic, cultural, environmental and hereditary factors. Several potential risk factors have been proposed for AUD in addition to alcohol consumption, including alcohol dehydrogenase2 (ADH2), acetaldehyde dehydrogenase2 (ALDH2), marital status, educational, occupational or past medical history (e.g. diabetes mellitus, hypertension, lung, digestive tract, or chronic liver disease) or smoking habits. The present study was performed to investigate the relationship between the aforementioned potential risk factors and AUD in Japan. A case-control study was performed on 153 male Japanese AUD patients and age-, gender-, or other confounder-matched controls to investigate the relation multivariately between ADH2, ALDH2 or alcohol drinking and AUD. Genomic DNA were extracted from nail clippings by the guanidium method, and genotyping of ADH2 and ALDH2 were performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Univariate analyses by the conditional logistic regression model revealed statistically significant odds ratios due to ADH2*1/1 genotype, ALDH2*1/1 genotype, middle school as the final school attended, longest occupations as farmers, fishermen, craftsmen, miners, production process or construction workers, and past histories of chronic liver disease and AUD. However, multivariate analyses under a hierarchically well-formulated model strategy with interaction and confounding assessment indicated that (i) heavy alcohol intake was a significant risk factor (odds ratio per 1.0 g of daily ethanol intake; 1.096, 95% confidence interval; 1.026-1.171) for developing AUD after adjusting for other confounders; and (ii) ADH2*1/1 genotype and ALDH2*1/1 genotype were not risk factors after adjusting for daily ethanol intake and other confounders. The present study shows that AUD was more directly and strongly associated with alcohol drinking than with alcohol metabolizing enzymes among male Japanese.     

Manganese accentuates adverse mental health effects associated with alcohol use disorders.

BACKGROUND: A population-based study on early neurotoxic effects of environmental exposure to manganese (Mn) enabled us to investigate the relation between blood Mn levels (MnB), alcohol consumption, and risk for alcohol use disorders (AUD) on mental health. METHODS: Participants were selected using a random stratified sampling procedure. Self-administered questionnaires provided data on alcohol consumption, sociodemographics, medical history, and lifestyle. Mood states were assessed with the Brief Symptom Inventory (BSI), and risk for AUD was surveyed using a behavioral screening questionnaire and categorized into no, low, and high risk. Of 297 participants, 253 current drinkers who had responded to all questions on alcohol use were retained. RESULTS: Psychologic distress increased with risk for AUD and alcohol consumption > or = 420 g/week. Higher MnB levels (> or =7.5 microg/L) intensified the relation between risk for AUD and BSI scale scores. The Prevalence odd ratios for positive cases of psychologic distress with risk for AUD, 1.98 [1.13-3.46], differed when divided by MnB strata: lower MnB: 1.34 [0.64-2.85]; higher MnB: 4.22 [1.65-10.77]. CONCLUSIONS: These findings suggest that higher levels of blood manganese significantly increase neuropsychiatric symptoms associated with risk for alcohol use disorders.     

朝鲜族、鄂伦春族醇代谢酶基因多态性与酒依赖的研究

目的了解醇脱氢酶（ＡＤＨ）和醛脱氢酶（ＡＬＤＨ）基因多态性与朝鲜族和鄂伦春族酒依赖发病的相互关系。方法采用耳血聚合酶链反应及等位基因特异性寡核苷酸杂交方法，检测ＡＤＨ和ＡＬＤＨ基因型在酒依赖患者（朝鲜族５５例，鄂伦春族３１例）与正常对照者（朝鲜族５０名，鄂伦春族３７名）人群中的分布频率。结果在酒依赖组与正常对照组之间，朝鲜族仅ＡＬＤＨ２基因频率的分布差异有非常显著性（Ｐ＜０．０１），而鄂伦春族的ＡＤＨ３基因频率分布和ＡＬＤＨ２基因频率分布的差异有非常显著性和显著性（Ｐ＜０．０１，Ｐ＜０．０５），两个民族的ＡＤＨ２基因频率分布差异均无显著性。结论提示朝鲜族酒依赖的发生与ＡＬＤＨ２基因有关，鄂伦春族则为ＡＬＤＨ２和ＡＤＨ３基因共同影响酒依赖的发生。     

Case-control study of multiple system atrophy.

The epidemiology of multiple system atrophy (MSA) is scarcely known, and risk factors have not been definitely identified. We investigated the effect of family history for neurodegenerative diseases and environmental factors on MSA risk in a multicentric case-control study. A total of 73 MSA patients (42 men, 31 women; age, 64.3 +/- 8.1 years; disease duration, 4.8 +/- 3.9 years), 146 hospital controls (84 men, 62 women; age, 64.9 +/- 8.4 years), and 73 population controls (42 men, 31 women; age, 63.7 +/- 8.9 years) matched for sex, age (+/-3 years), and province of residence were enrolled consecutively at seven neurological centers from 1 January 1994 to 31 July 1998. The following variables were investigated: family history of neurodegenerative diseases, education, smoking habits, hobbies, and occupational history. Occupational history of farming was significantly more frequent among MSA cases than controls (OR adj = 2.52; 95% CI, 1.25 to 5.07, MSA vs. hospital controls; OR adj = 4.53; 95% CI, 1.68 to12.2, MSA cases vs. population controls). A dose-response analysis for years of farming corroborated this association. We recently found that smoking is significantly less frequent among MSA cases than controls (Vanacore et al. [2000] Neurology 54:114-119). Here, we report that the effects of farming and smoking on MSA risk do not interact. Our results suggest that occupational history of farming is a risk factor for MSA. Smoking and farming seem to influence MSA risk independently. Further epidemiological studies might provide clues on the etiopathogenesis of MSA.     

Elevation of blood beta-carboline alkaloids in essential tremor

BACKGROUND: beta-Carboline alkaloids are normal body constituents but are also potent tremor-producing chemicals that are naturally present in the food chain. OBJECTIVE: To explore the hypothesis that high concentrations of beta-carboline alkaloids are associated with essential tremor (ET). METHODS: One hundred cases and 100 controls were frequency matched on age, sex, and ethnicity. Blood concentrations of harmane and harmine were quantified by high-performance liquid chromatography, blinded to clinical information. RESULTS: The mean log blood concentration of harmane was higher in cases than controls (0.72 +/- 0.53 vs 0.51 +/- 0.64 g(-10)/mL; p = 0.01). A nonparametric test on nontransformed data (median harmane = 5.21 g(-10)/mL in cases and 2.28 g(-10)/mL in controls) confirmed this difference (p = 0.005). The mean log blood concentration of harmine was 0.20 +/- 0.48 g(-10)/mL in cases and 0.10 +/- 0.65 g (-10)/mL in controls (p = 0.20). Log harmane concentrations were stratified based on the median value; 62% of cases vs 39% of controls had a high log harmane concentration (p = 0.001). Mean log harmane concentration was similar in the cases with (0.74 +/- 0.58 g(-10)/mL) and without (0.71 +/- 0.50 g(-10)/mL) an affected relative (p = 0.83). CONCLUSIONS: Blood concentrations of harmane were measured in ET cases compared with controls. Concentrations were elevated in cases with and without a family history of ET.     

中国蒙,汉族酒依赖与醇脱氢酶和醛脱氢酶基因多态性的相关研究

为探讨醇脱氢酶（ＡＤＨ）基因和醛脱氢酶（ＡＬＤＨ）基因多态性与酒依赖患病的相互关系，用耳血干血痕聚合酶链反应、等位基因特异性寡核苷酸探针方法，检测乙醇代谢酶ＡＤＨ和ＡＬＤＨ基因型在我国蒙、汉民族酒依赖与非酒依赖者中分布频率。结果显示在酒依赖组（汉族５２例，蒙族３１例）与正常对照组（汉族４８例，蒙族３５例）之间：汉族的ＡＬＤＨ２基因型频率与等位基因频率的分布差异有非常显著性（Ｐ＜０．０１），而蒙族则表示为ＡＤＨ２基因型频率与等位基因频率的分布差异有非常显著性（Ｐ＜０．０１）。这提示汉族酒依赖的发病与ＡＬＤＨ２基因有关，蒙族则与ＡＤＨ２基因有关。     

Clinical characteristics of bipolar I patients according to their family history of affective disorders

BACKGROUND: The familial nature of bipolar disorder has been well described and multiple genes are probably involved in most or all cases. Each gene contributes equally to a bipolar phenotype and it may contribute to clinical characteristics. However, the genetic transmission of bipolar disorder remained undetermined up to now, partly due to clinical and genetically heterogeneity. In Tunisia, genetic study will profit from specific interests and advantages: the high rates of consanguinity, the existence of large families, and the relative geographical stability of the population. OBJECTIVE: The aim of this study was to compare clinical characteristics of familial and nonfamilial bipolar I disorder. METHOD: One hundred and thirty subjects met DSM-IV criteria for a bipolar I disorder; they were recruited and divided into groups according to their family history of affective disorders. Group 1 with a familial history group, comporting bipolar I patients with a family history of affective disorders in first and second degree relatives (n = 76; 52 males and 24 females, mean age = 37.2 +/- 10.7 years) was compared to group 2 (nonfamilial history group), comporting bipolar I patients without a family history of affective disorders (n = 54; 29 males and 25 females, mean age = 38.1 +/- 10.9 years). Available information was obtained from a structured clinical interview, collateral history, and medical records. The family investigation permitted completion of genealogies over three generations. The comparison of the two groups was based on the clinical characteristics (age at onset, numbers of affective episodes, nature and severity of the last affective episode,...). RESULTS: There were no significant differences between the two groups concerning demographic and social features, with the exception of professional activity. Indeed 30.2% of patients with a family history of affective disorders were unemployed versus 12.9% of patients without a family history of affective disorders (p = 0.02). Bipolar I patients with a family history of affective disorders were characterised by an early age at onset of the first episode (before 20 years) (48.7 versus 24.0%; p = 0.004), a high frequency of affective episodes (8.1 +/- 3.6 versus 6.0 +/- 3.5; p = 0.002) and had been more often hospitalised than patients without a family history of affective disorders (5.7 +/- 3.0 versus 4.7 +/- 3.0; p = 0.06). No significant differences were found concerning the nature of the first affective episode in bipolar I patients with or without a family history of affective disorders. Eleven women had developed their first affective episode during the puerperal period; eight of whom had a family history of affective disorders (p = 0.07). The last affective episode was significantly more severe (94.8 versus 77.8%; p = 0.003) and more often associated with psychotic features (55.3 versus 35.2%; p = 0.02) in patients with a family history of affective disorders. After multiple regression, the high frequency of affective episodes and the severity of last episode were more related with a family history of affective disorders. CONCLUSION: The results of our study provide evidence of familiality for some clinical characteristics which can be useful as phenotypic measures in future molecular genetic studies.     

Factors associated with temporal priority in comorbid bipolar I disorder and alcohol use disorders: Results from the national epidemiologic survey on alcohol and related conditions

OBJECTIVE: To compare illness characteristics, comorbidities, treatment utilization, and family history among individuals with comorbid bipolar I disorder and alcohol use disorders (AUD) based on temporal priority of onset. METHOD: The 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions identified respondents with lifetime comorbid bipolar I disorder and AUD for whom AUD were antecedent (Alcohol First; N = 311), the onset of the 2 conditions occurred in the same year (Same Year; N = 113), or bipolar I disorder was antecedent (Bipolar First; N = 233). Diagnoses were generated using the National Institute on Alcohol Abuse and Alcoholism Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version. This study examined between-group differences in bipolar I- and AUD-related variables. RESULTS: Bipolar First respondents were most likely to experience prolonged manic episodes. There were no differences in the 12-month prevalence of bipolar I disorder among respondents with prior history of bipolar I disorder. The 12-month prevalence of AUD among respondents with prior history of AUD was lower among Alcohol First respondents compared to Same Year or Bipolar First respondents. Same Year respondents were most likely to seek AUD treatment and reported comparatively short latency between onset and treatment of both bipolar I disorder and AUD. The prevalence of family history of comorbid depression and AUD was greatest among Same Year respondents. Same Year respondents also showed the lowest prevalence of anxiety disorders. Overall psychosocial functioning was similar across groups. CONCLUSION: Temporal priority in comorbid bipolar I disorder and AUD is associated with several significant between-group differences in features of bipolar I disorder and AUD severity, treatment utilization, other comorbidities, and family history. Same-year onset of bipolar I disorder and AUD may be a marker of a specific subtype of bipolar I-AUD comorbidity. Potential implications of these findings are discussed.     

Elevated blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations in essential tremor

Essential tremor (ET) is a widespread late-life neurological disease. Genetic and environmental factors likely play an etiological role. Harmane (1-methyl-9H-pyrido[3,4-b]indole) is a potent tremor-producing neurotoxin. In 2002, we demonstrated elevated blood harmane concentrations in an initial sample of 100 ET cases compared to 100 controls. Between 2002 and 2007, we assembled a new and larger sample of ET cases and controls. We now attempt to replicate our previous findings. Cases and controls were frequency-matched on age, gender, and race. Blood harmane concentrations were quantified by high-performance liquid chromatography. Subjects comprised 150 ET cases and 135 controls (mean age 65.3+/-15.5 vs. 65.5+/-14.2 years, p=0.94). Mean log blood harmane concentration was approximately 50% higher in cases than controls (0.50+/-0.54g(-10)/ml vs. 0.35+/-0.62g(-10)/ml, p=0.038). In a logistic regression analysis, log blood harmane concentration was associated with ET (OR(adjusted) 1.56, 95% CI 1.01-2.42, p=0.04), and odds of ET was 1.90 (95% CI 1.07-3.39, p=0.029) in the highest versus lowest log blood harmane tertile. Log blood harmane was highest in ET cases with familial ET (0.53+/-0.57g(-10)/ml), intermediate in cases with sporadic ET (0.43+/-0.45g(-10)/ml) and lowest in controls (0.35+/-0.62g(-10)/ml) (test for trend, p=0.026). Blood harmane appears to be elevated in ET. The higher concentrations in familial ET suggests that the mechanism may involve genetic factors.