RESUMO
The multi-pass transmembrane protein ACCELERATED CELL DEATH 6 (ACD6) is an immune regulator in Arabidopsis thaliana with an unclear biochemical mode of action. We have identified two loci, MODULATOR OF HYPERACTIVE ACD6 1 (MHA1) and its paralog MHA1-LIKE (MHA1L), that code for â¼7 kDa proteins, which differentially interact with specific ACD6 variants. MHA1L enhances the accumulation of an ACD6 complex, thereby increasing the activity of the ACD6 standard allele for regulating plant growth and defenses. The intracellular ankyrin repeats of ACD6 are structurally similar to those found in mammalian ion channels. Several lines of evidence link increased ACD6 activity to enhanced calcium influx, with MHA1L as a direct regulator of ACD6, indicating that peptide-regulated ion channels are not restricted to animals.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Anquirinas/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Morte Celular , Canais Iônicos/genética , Canais Iônicos/metabolismo , Imunidade Vegetal/genéticaRESUMO
Repeated herbicide applications in agricultural fields exert strong selection on weeds such as blackgrass (Alopecurus myosuroides), which is a major threat for temperate climate cereal crops. This inadvertent selection pressure provides an opportunity for investigating the underlying genetic mechanisms and evolutionary processes of rapid adaptation, which can occur both through mutations in the direct targets of herbicides and through changes in other, often metabolic, pathways, known as non-target-site resistance. How much target-site resistance (TSR) relies on de novo mutations vs. standing variation is important for developing strategies to manage herbicide resistance. We first generated a chromosome-level reference genome for A. myosuroides for population genomic studies of herbicide resistance and genome-wide diversity across Europe in this species. Next, through empirical data in the form of highly accurate long-read amplicons of alleles encoding acetyl-CoA carboxylase (ACCase) and acetolactate synthase (ALS) variants, we showed that most populations with resistance due to TSR mutations-23 out of 27 and six out of nine populations for ACCase and ALS, respectively-contained at least two TSR haplotypes, indicating that soft sweeps are the norm. Finally, through forward-in-time simulations, we inferred that TSR is likely to mainly result from standing genetic variation, with only a minor role for de novo mutations.
Assuntos
Resistência a Herbicidas , Herbicidas , Resistência a Herbicidas/genética , Poaceae/genética , Poaceae/metabolismo , Mutação , Haplótipos , Europa (Continente) , Herbicidas/farmacologia , Acetil-CoA Carboxilase/genética , Acetil-CoA Carboxilase/metabolismoRESUMO
Plants integrate seasonal cues such as temperature and day length to optimally adjust their flowering time to the environment. Compared to the control of flowering before and after winter by the vernalization and day length pathways, mechanisms that delay or promote flowering during a transient cool or warm period, especially during spring, are less well understood. Due to global warming, understanding this ambient temperature pathway has gained increasing importance. In Arabidopsis thaliana, FLOWERING LOCUS M (FLM) is a critical flowering regulator of the ambient temperature pathway. FLM is alternatively spliced in a temperature-dependent manner and the two predominant splice variants, FLM-ß and FLM-δ, can repress and activate flowering in the genetic background of the A. thaliana reference accession Columbia-0. The relevance of this regulatory mechanism for the environmental adaptation across the entire range of the species is, however, unknown. Here, we identify insertion polymorphisms in the first intron of FLM as causative for accelerated flowering in many natural A. thaliana accessions, especially in cool (15°C) temperatures. We present evidence for a potential adaptive role of this structural variation and link it specifically to changes in the abundance of FLM-ß. Our results may allow predicting flowering in response to ambient temperatures in the Brassicaceae.
Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Flores/genética , Proteínas de Domínio MADS/genética , Mutagênese Insercional/genética , Processamento Alternativo/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/biossíntese , Regulação da Expressão Gênica de Plantas , Aquecimento Global , Proteínas de Domínio MADS/biossíntese , Polimorfismo Genético , Estações do Ano , TemperaturaRESUMO
PURPOSE: Psychotic symptoms in Parkinson's disease (PD) caused by dopamimetic treatment are a relevant clinical problem. As clozapine does not cause extrapyramidal side effects, it is suitable for treatment of dopamimetic psychosis. The main aim of the present study was (1) to establish an indication-specific recommendation for therapeutic reference range of clozapine among patients with dopamimetic psychosis in PD and related disorders. Secondary goals were (2) to test whether clozapine therapy is safe and calculable despite pharmacokinetic changes expected in the study population and (3) to assess influencing variables on clozapine serum levels. METHODS: We carried out a retrospective chart review of patients suffering from dopamimetic psychosis as well as Lewy body dementia treated with clozapine. We extracted demographic and clinical data as well as results from therapeutic drug monitoring that was carried out via high-performance liquid chromatography in order to analyse clozapine and norclozapine serum concentrations. RESULTS: n = 35 patients could be identified and were included in the study. Mean age was 72.4 years. Clozapine treatment for patients with dopamimetic psychosis in PD and related disorders seems to be safe and calculable. Mean clozapine serum concentration was 77.9 ng/ml (SD 63.4 ng/ml). Clozapine dose is significantly correlated with serum clozapine concentration (r = 0.35; R (2) = 0.122). Women showed lower clozapine serum concentrations although they received higher weight-corrected clozapine doses. CONCLUSIONS: We suggest an orienting indication-specific therapeutic reference range of 15-141 ng/ml among PD patients with dopamimetic psychosis. Therapeutic drug monitoring is recommended and might help to minimize the risk of adverse events by screening for unexpectedly high serum concentrations of clozapine.
Assuntos
Antipsicóticos/sangue , Clozapina/sangue , Doença de Parkinson/sangue , Transtornos Psicóticos/sangue , Idoso , Idoso de 80 Anos ou mais , Antipsicóticos/farmacocinética , Antipsicóticos/uso terapêutico , Clozapina/farmacocinética , Clozapina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/tratamento farmacológico , Transtornos Psicóticos/tratamento farmacológicoRESUMO
BACKGROUND: Before 2010, Amaranthus tuberculatus (Moq.) J. D. Sauer was barely known to farmers and stakeholders in Italy. Since then, several populations resistant to acetolactate synthase (ALS)-inhibiting herbicides have been collected. In most populations, a known target site resistance-endowing mutation was found, a Trp to Leu substitution at position 574 of the ALS gene, but it was unclear whether they had evolved resistance independently or not. The aims of the work were (i) to elucidate the population structure of Italian ALS-resistant A. tuberculatus populations, and (ii) to analyze the ALS haplotypes of the various populations to determine whether resistance arose multiple times independently. RESULTS: In order to determine the population structure of eight A. tuberculatus populations, eight previously described microsatellite loci were used. Two ancestors were found: three populations derived from one, and five from the other. In the 4-kb ALS region of the genome, including the 2-kb coding region, 389 single nucleotide polymorphisms were found. In silico haplotype estimation was used to reconstruct the sequence of three distinct haplotypes carrying the Trp574Leu mutation. In addition, no mutation was found in 83% of plants of a single population. CONCLUSIONS: (i) Resistance must have arisen independently at least three times; (ii) at least one population was already resistant to ALS inhibitors when introduced in Italy; (iii) a single haplotype with a Trp574Leu mutation was shared among six populations, probably because of broad seed dispersal; and (iv) one population likely evolved nontarget site ALS inhibitors resistance. © 2021 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Assuntos
Acetolactato Sintase , Amaranthus , Herbicidas , Acetolactato Sintase/genética , Amaranthus/genética , Resistência a Herbicidas/genética , Herbicidas/farmacologia , ItáliaRESUMO
Cool ambient temperatures are major cues determining flowering time in spring. The mechanisms promoting or delaying flowering in response to ambient temperature changes are only beginning to be understood. In Arabidopsis thaliana, FLOWERING LOCUS M (FLM) regulates flowering in the ambient temperature range and FLM is transcribed and alternatively spliced in a temperature-dependent manner. We identify polymorphic promoter and intronic sequences required for FLM expression and splicing. In transgenic experiments covering 69% of the available sequence variation in two distinct sites, we show that variation in the abundance of the FLM-ß splice form strictly correlate (R2 = 0.94) with flowering time over an extended vegetative period. The FLM polymorphisms lead to changes in FLM expression (PRO2+) but may also affect FLM intron 1 splicing (INT6+). This information could serve to buffer the anticipated negative effects on agricultural systems and flowering that may occur during climate change.
Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Arabidopsis/efeitos da radiação , Flores/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas , Haplótipos , Proteínas de Domínio MADS/metabolismo , Temperatura , Splicing de RNAAssuntos
Lactação/efeitos dos fármacos , Leite Humano/química , Leite Humano/efeitos dos fármacos , Piperazinas/uso terapêutico , Quinolonas/uso terapêutico , Adulto , Aripiprazol , Aleitamento Materno/efeitos adversos , Feminino , Humanos , Recém-Nascido , Lactação/metabolismo , Masculino , Leite Humano/metabolismo , Piperazinas/efeitos adversos , Piperazinas/análise , Gravidez , Quinolonas/efeitos adversos , Quinolonas/análise , Esquizofrenia/tratamento farmacológico , Esquizofrenia/metabolismoRESUMO
BACKGROUND: Norepinephrine and dopamine mediate important aspects of alcoholism and alcohol withdrawal. Dopamine-beta-hydroxylase (DbetaH) converts dopamine to norepinephrine. A recent study demonstrated a strong association between variance in plasma DbetaH activity and a novel polymorphism (DBH-1021C-->T) at the structural locus (DBH) encoding DbetaH protein. METHODS: Our study investigated whether the DBH-1021C-->T polymorphism and plasma DbetaH activity were associated with alcoholism or with delirium tremens (DT) during alcohol withdrawal by analyzing 207 German alcoholic and 102 healthy control subjects. We also examined the influence of the polymorphism on enzyme activity. RESULTS: Mean (+SD) plasma DbetaH activity measured in alcoholic subjects abstinent was significantly lower than that observed in control (27.7 + 16.7 vs. 35.6 + 18.8; p =.01). It did not differ between subjects with DT during withdrawal and subjects with mild withdrawal symptoms. The T allele of the DBH-1021C-->T polymorphism was significantly associated with lower plasma DbetaH activity. None of the alleles or genotypes were associated with alcoholism or DT. CONCLUSIONS: The data indicate that the alcoholism-related reduction in plasma DbetaH activity is independent of genotype at DBH-1021C-->T and replicate the finding that DBH-1021C-->T is strongly associated with plasma DbetaH activity in a native Western European population.
Assuntos
Alcoolismo/genética , Dopamina beta-Hidroxilase/genética , Adulto , Delirium por Abstinência Alcoólica/sangue , Alcoolismo/sangue , Alelos , Dopamina beta-Hidroxilase/sangue , Genótipo , Alemanha , Heterozigoto , Humanos , Masculino , Norepinefrina/sangue , Norepinefrina/genética , Polimorfismo Genético , Síndrome de Abstinência a Substâncias/sangueRESUMO
The central dopamine system seems to influence addictive disorders. Plasma homovanillic acid (HVA) is an indicator of central dopaminergic activity. In this study the hypothesis that plasma HVA is associated with alcoholism or with delirium tremens (DT) during alcohol withdrawal was tested. A functional genetic polymorphism of the enzyme catechol-O-methyltransferase (COMT) that participates in converting dopamine into its final metabolite HVA was investigated for an association with alcoholism or DT during alcohol withdrawal. In addition, a relation between the functional polymorphism of COMT and plasma HVA concentrations was studied. Plasma HVA concentrations and COMT genotypes were determined in 142 German alcoholics and 101 German healthy controls. Alcoholic patients were examined after a minimum of 3 weeks after cessation of drinking. Mean plasma HVA concentrations were significantly lower in alcoholic patients compared to healthy controls. A group of alcoholics with a history of DT during alcohol withdrawal (n=62) did not differ significantly in plasma HVA concentrations from alcoholics with a history of only mild withdrawal symptoms (n=67). The functional polymorphism of the human COMT gene was neither significantly associated with the diagnosis of alcoholism or DT during alcohol withdrawal nor with plasma HVA concentrations.
Assuntos
Alcoolismo/sangue , Alcoolismo/genética , Catecol O-Metiltransferase/genética , Ácido Homovanílico/sangue , Polimorfismo Genético/genética , Adulto , Delirium por Abstinência Alcoólica/sangue , Delirium por Abstinência Alcoólica/genética , Análise de Variância , Intervalos de Confiança , Feminino , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , Razão de ChancesRESUMO
OBJECTIVE: Subjective quality of sleep is impaired in smokers compared with non-smokers, but there is only limited evidence from methodologically sound studies about differences in polysomnography (PSG) sleep characteristics. Therefore, this study used PSG to evaluate sleep in smokers and non-smokers while controlling for other parameters that affect sleep. METHODS: After an adaptation night, PSG sleep laboratory data were obtained from 44 smokers (29 men and 15 women, median age 29.6 years) and compared with PSG data from 44 healthy, sex- and age-matched never smokers. Exclusion criteria were alcohol or other substance abuse, psychiatric or endocrine diseases, and treatment with any kind of psychotropic medication. Nicotine and cotinine plasma levels were measured (in the smoking group) and subjective sleep quality assessed in both groups. RESULTS: The smokers had a Fagerström tolerance score of 6.4, consumed an average of 21.2 cigarettes per day and had been smoking for 13.1 years (median). Smokers had a shorter sleep period time, longer sleep latency, higher rapid eye movement sleep density, more sleep apneas and leg movements in sleep than non-smokers. There were no differences regarding parameters of spectral analysis of the sleep electroencephalogram as well as in the sleep efficiency measured by PSG. Nevertheless smokers rated their sleep efficiency lower on the Pittsburgh Sleep Quality Index compared with non-smoking individuals, but no differences were detected on the SF-A. Plasma cotinine level correlated negatively with slow wave sleep in the smoking group. CONCLUSIONS: Smokers showed a number of insomnia-like sleep impairments. The findings suggest that it is important for sleep researchers to control smoking status in their analyses. Further research should focus on the causes and consequences of impaired sleep during tobacco cessation, as sleep disturbances are a known risk factor for early relapse after initial tobacco abstinence.
Assuntos
Sono/efeitos dos fármacos , Fumar/efeitos adversos , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Polissonografia , Sono/fisiologia , Fases do Sono/efeitos dos fármacos , Fases do Sono/fisiologia , Fumar/fisiopatologiaRESUMO
INTRODUCTION: Delirium tremens and withdrawal seizures are serious complications of an alcohol withdrawal syndrome. This review presents the diagnostic procedures required in case of the occurrence of a withdrawal seizure and delirium tremens as well as possible treatment options including prophylactic medication regimen for alcohol withdrawal syndrome. Furthermore non-pharmacological procedures accompanying delirium tremens and a potential integration of viewing videotapes of delirium tremens in the course of alcohol-specific therapy are discussed. METHODS: A systematic literature research using Pubmed has been carried out to find recent studies and review articles dealing with alcohol withdrawal syndrome. RESULTS AND DISCUSSION: Regarding the diagnostic algorithm in case of the occurrence of a withdrawal seizure or a delirium tremens basic diagnostic procedures and special diagnostics including neuro-imaging or cerebrospinal fluid puncture depending on patients' clinical condition have to be considered. Sedatives are important in treatment of alcohol withdrawal seizures and delirium tremens as well as in the prophylaxis of alcohol withdrawal syndrome. A long-lasting prescription of anticonvulsant medication in patients suffering from withdrawal seizure should be considered critically and can be carried out only under certain conditions.
Assuntos
Delirium por Abstinência Alcoólica/diagnóstico , Delirium por Abstinência Alcoólica/reabilitação , Convulsões por Abstinência de Álcool/diagnóstico , Convulsões por Abstinência de Álcool/reabilitação , Alcoolismo/reabilitação , Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas Adrenérgicos beta/efeitos adversos , Delirium por Abstinência Alcoólica/classificação , Delirium por Abstinência Alcoólica/prevenção & controle , Convulsões por Abstinência de Álcool/classificação , Convulsões por Abstinência de Álcool/prevenção & controle , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/efeitos adversos , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Benzodiazepinas/administração & dosagem , Benzodiazepinas/efeitos adversos , Clordiazepóxido/administração & dosagem , Clordiazepóxido/efeitos adversos , Clormetiazol/administração & dosagem , Clormetiazol/efeitos adversos , Terapia Combinada , Comorbidade , Diagnóstico Diferencial , Esquema de Medicação , Interações Medicamentosas , Etanol/sangue , Etanol/toxicidade , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Prevenção SecundáriaRESUMO
Addiction research focusing on homocysteine metabolism and its association with aspects of alcohol dependence has revealed important findings. Recent literature on this topic has been taken into account for the review provided. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the homocysteine metabolism. Plasma homocysteine levels are influenced by the single-nucleotide polymorphism (SNP) MTHFR C677T. Besides genetic factors, environmental factors have an impact on homocysteine plasma levels too. Thus, chronic alcohol intake is associated with elevated homocysteine plasma concentrations. Elevation of plasma homocysteine concentration is considered as a predictor for the occurrence of alcohol withdrawal seizures and--as homocysteine is a cardiovascular risk factor--might contribute to the higher risk for myocardial infarction among alcohol dependent patients. Homocysteine acts as an N-methyl-D-aspartate (NMDA) receptor agonist and has excitotoxic effects. Furthermore, it has been demonstrated that homocysteine has neurotoxic effects especially on dopaminergic neurons. As the rewarding effects of alcohol are mediated by the dopaminergic system, a homocysteine-dependent impairment of the reward system possibly leads to an altered drinking behaviour according to the deficit hypothesis of addiction. Homocysteine is involved in the metabolism of methyl groups and DNA-methylation plays a role in regulation of gene expression. Therefore it has been suggested that homocysteine is an important epigenetic factor. It remains to be determined whether alcohol dependent patients benefit from homocysteine lowering strategies, e.g., via supplementation of folate, vitamin B6 and B12. In this respect it is not clear yet, if a supplementation therapy can reduce the risk for the occurrence of alcohol withdrawal seizures.
Assuntos
Convulsões por Abstinência de Álcool/enzimologia , Convulsões por Abstinência de Álcool/genética , Alcoolismo/enzimologia , Alcoolismo/genética , Alelos , Epigênese Genética/genética , Etanol/toxicidade , Homocisteína/sangue , Metilenotetra-Hidrofolato Desidrogenase (NADP)/genética , Polimorfismo de Nucleotídeo Único/genética , Meio Social , Convulsões por Abstinência de Álcool/tratamento farmacológico , Alcoolismo/reabilitação , Metilação de DNA/genética , Dopamina/fisiologia , Ácido Fólico/uso terapêutico , Regulação Enzimológica da Expressão Gênica/genética , Humanos , Infarto do Miocárdio/enzimologia , Infarto do Miocárdio/genética , Receptores de N-Metil-D-Aspartato/agonistas , Recompensa , Fatores de Risco , Vitamina B 12/uso terapêutico , Vitamina B 6/uso terapêuticoRESUMO
Postpartum psychosis constitutes a severe complication that entails risk for both mother and child. Little is known about the use of olanzapine in the treatment of postpartum psychosis. In previous studies, it has been reported on mothers receiving relatively low doses of olanzapine. We report a 38-year-old patient who was admitted to the hospital for an acute psychotic exacerbation. She was breast feeding her 5-month-old child, and she wished to continue breast feeding. Olanzapine treatment was started with a daily dosage of 15 mg. The weight-corrected maternal dose was 270 mug/kg. The olanzapine concentration in the mother's plasma was 24 ng/mL. The analysis of olanzapine in breast milk applying two different high-performance liquid chromatography procedures revealed similar results: 12.2 ng/g without and 11.5 ng/g with additional hydrochloric acid extraction, respectively. In addition, breast milk of an unmedicated mother was used for establishing the analytical procedure so that the validity of the results was better confirmed. The milk-plasma ratio arising from our data was 0.5, and the relative infant dose was 0.3%. The olanzapine concentration was below the limit of detection (<5 ng/mL) in the infant's plasma sample. No adverse effects were noticed, and the mother experienced a rapid improvement in her psychopathology during her hospital stay. In future studies, long-term follow-up of both mother and child would be useful.
Assuntos
Antipsicóticos/uso terapêutico , Benzodiazepinas/uso terapêutico , Aleitamento Materno , Adulto , Antipsicóticos/análise , Antipsicóticos/sangue , Benzodiazepinas/análise , Benzodiazepinas/sangue , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Lactente , Leite Humano/química , Olanzapina , Período Pós-Parto , Esquizofrenia Paranoide/tratamento farmacológicoRESUMO
The enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) synthesizes 5-methyltetrahydrofolate. It plays a critical role in homocysteine metabolism. A high impact of MTHFR C677T polymorphism on plasma homocysteine levels has been observed among alcoholics. Recent studies indicate that homocysteine has toxic effects on dopaminergic neurons. Thus it lowers levels of homovanillic acid (HVA) in the striatal region in rats. Alcoholics had significantly lower plasma HVA concentrations compared with healthy controls. Aim of this study is to elucidate whether HVA plasma levels in alcoholics are influenced by MTHFR C677T polymorphism. A total of 142 alcohol-dependent patients and 101 healthy controls were examined regarding plasma HVA concentration and MTHFR C677T genotype. Blood samples of alcoholics were obtained after a minimum of 22 days of abstinence. Among alcohol-dependent patients MTHFR C677T polymorphism was significantly associated with plasma HVA levels: carriers of MTHFR C677T T-allele had significantly lower HVA plasma levels compared with homozygote carriers of C-allele: 11.9 ng/ml versus 14.4 ng/ml (chi2: 5.39; P = 0.02). In healthy control subjects plasma HVA levels did not differ significantly between MTHFR C677T T-allele carriers and homozygote carriers of C-allele: 15.1 ng/ml versus 15.3 ng/ml (chi2: 0.04; P = 0.82). The data suggest an influence of MTHFR C677T polymorphism on plasma HVA among alcohol-dependent patients. This might be due to neurotoxic effects of homocysteine on the dopaminergic system or direct impairment of monoamine metabolism. Future studies should try to elucidate whether this effect is reversible during alcohol abstinence.
Assuntos
Alcoolismo/genética , Genótipo , Ácido Homovanílico/sangue , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo Genético/genética , Adulto , Alcoolismo/sangue , Alelos , Dopamina/fisiologia , Feminino , Triagem de Portadores Genéticos , Homocisteína/sangue , Homozigoto , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
As the inhibitory neurotransmitter gamma aminobutyric acid (GABA) modulates ethanol consumption, alcohol withdrawal symptoms and seizure generation by interacting with the GABAB receptor, the genes encoding for the GABAB receptor can be considered as candidate genes for alcoholism and alcohol withdrawal seizures (AWS). As the polymorphism GABABR1 T1974C[rs29230] of the GABAB receptor gene had been associated with alcoholism and EEG abnormalities in prior studies, the present examination investigated if the polymorphism is associated with the diagnosis of alcoholism or AWS. After genotyping the allele and genotype frequencies of a group of alcoholics with a history of AWS (n = 69) were compared with the results of a group of alcoholics with only mild withdrawal symptoms (n = 97). Additionally a group of healthy controls (n = 101) was compared with individuals with the diagnosis of alcoholism (n = 220). As no significant differences were found between the compared groups, this study gave no further evidence for GABABR1 T1974C[rs29230] as a candidate for alcoholism or AWS.
Assuntos
Alcoolismo/diagnóstico , Alcoolismo/genética , Etanol/efeitos adversos , Polimorfismo Genético/genética , Receptores de GABA-B/genética , Convulsões/etiologia , Síndrome de Abstinência a Substâncias/complicações , Síndrome de Abstinência a Substâncias/etiologia , Adulto , Alelos , Feminino , Genótipo , Humanos , Masculino , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Elevated homocysteine plasma levels are considered as a risk factor for the occurrence of seizures during alcohol withdrawal. Homocysteine plasma concentrations seem to be influenced by the methylenetetrahydrofolate reductase (MTHFR) C677T-polymorphism. It was investigated whether the T-allele of the MTHFR C677T-polymorphism is associated with alcohol dependence, alcohol withdrawal seizure (WS), or the daily amount of alcohol consumption. METHODS: A group of 102 healthy controls and 221 alcoholic patients, including 97 patients with a history of mild withdrawal symptoms (MWS) and 70 patients with a history of alcohol WS, were genotyped, and personal data were collected for statistical evaluation in a case-control design. RESULTS: The T-allele is significantly associated with WS by comparing alcoholic patients with a history of WS (T-allele frequency: 0.39) and healthy controls (T-allele frequency: 0.28) (p=0.03). Although there was no significant difference between alcoholic patients with only MWS and alcoholic patients with a history of WS, a trend for the T-allele frequency among the analyzed subgroups was noticed: T-allele frequency increased from f(T)=0.28 in healthy controls to f(T)=0.33 in alcoholic patients with MWS up to f(T)=0.40 in alcohol-dependent men having a WS. Differences between healthy male controls and male alcoholic patients concerning the T-allele frequency also turned out to be significant [f(T)=0.27 vs f(T)=0.37; p=0.03]. Daily alcohol intake was independent of T-allele carrier status in alcohol-dependent patients. CONCLUSION: The present study suggests an influence of the MTHFR C677T-polymorphism on the etiology of alcohol WS and alcohol dependence in men in a western European population. An influence of MTHFR C677T on the daily amount of alcohol intake before admission among alcohol-dependent patients could not be shown.
Assuntos
Convulsões por Abstinência de Álcool/genética , Alcoolismo/genética , Predisposição Genética para Doença , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Consumo de Bebidas Alcoólicas/genética , Estudos de Casos e Controles , Citosina , Feminino , Frequência do Gene , Genótipo , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , TiminaRESUMO
AIMS: It was investigated whether the allele A9 of the dopamine transporter gene (DAT1; SLC6A3) is associated with alcoholism, delirium tremens (DT), alcohol withdrawal seizures (AWS), or the daily alcohol intake. METHODS: A group of 102 healthy subjects and 216 alcoholics, including 97 patients with a history of mild withdrawal symptoms, 65 with a history of AWS and 83 with a history of DT were genotyped and personal data were achieved for statistical evaluation in a case-control design. RESULTS: The frequency of individuals carrying the allele A9 [f(A9+)] was significantly higher (P = 0.01) in the group of alcoholics [f(A9+) = 0.48] compared with healthy controls [f(A9+) = 0.32]. There was no significant association of the allele A9 with severe withdrawal symptoms or the daily amount of alcohol consumed. CONCLUSIONS: Our results reveal that the allele A9 is strongly associated with alcoholism but not with withdrawal symptoms or daily alcohol intake.