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Association between a functional polymorphism in the monoamine oxidase A gene promoter and major depressive disorder 总被引:4,自引:0,他引:4
Schulze TG Müller DJ Krauss H Scherk H Ohlraun S Syagailo YV Windemuth C Neidt H Grässle M Papassotiropoulos A Heun R Nöthen MM Maier W Lesch KP Rietschel M 《American journal of medical genetics》2000,96(6):801-803
Various polymorphisms of the X-chromosomal monoamine oxidase A (MAO-A) gene were investigated for association with affective disorders. However, none of the studied variants could consistently be associated with either major depressive or bipolar affective disorder. Recently, a positive association between panic disorder and a novel functional repeat polymorphism in the MAO-A gene promoter, with the longer alleles being more active, was reported. Since monoaminergic neurotransmission is supposed to play an important role in affective disorders, we investigated a potential association of this polymorphism with major depressive illness in a sample of 146 unrelated patients of German descent and a control group of 101 individuals with a negative life history for affective disorders. Similarly to the recent findings in panic disorder, we observed a significantly increased frequency of genotypes containing only long alleles in female patients with recurrent major depression in comparison with age- and sex-matched controls. Thus, our data suggest that an excess of high-activity MAO-A gene promoter alleles resulting in an elevated MAO-A activity is a risk factor for major depressive disorder in females. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:801-803, 2000. 相似文献
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To ascertain whether mood disorders, including bipolar and unipolar, are genetically associated with the monoamine oxidase A (MAOA) or monoamine oxidase B (MAOB) gene in the Chinese population, 132 cases of mood disorder and 88 normal controls were genotyped for the MAOA(CA)n, MAOB(GT)n, and MAOB(TG)n loci by the method of amplification fragment length polymorphism. Among 132 cases with mood disorder, eight alleles (size: 112-126 bp) of locus MAOA(CA)n, 12 alleles (size: 168-198 bp) of locus MAOB(GT)n, and nine alleles (size: 195-213 bp) of locus MAOB(TG)n were observed. Comparison of the allele frequency of the three loci showed no difference between mood disorder cases and normal controls on average. When each group was stratified into several subgroups, significant differences were found. On the MAOA(CA)n locus, the frequency of 116 bp allele was higher in the female bipolar disorder cases (0.2581) compared with that in the female unipolar disorder patients (0.1154) (Z=2.15, p<0. 05). On the MAOB(GT)n locus, the frequency of 180 bp allele was higher in bipolar disorder patients (0.1579) than that in normal controls (0.0678) (Z=2.05, p<0.05). The frequency of this allele was even higher in female bipolar disorder patients (0.1719) than that in female normal controls (0.0541). On the MAOB(TG)n locus, the frequency of 205 bp allele was higher in female bipolar disorder patients (0.6406) than that in female normal controls (0.4375) (Z=2. 17, p<0.05). For the unipolar disorder patients, the frequency of this allele was higher in female cases (0.5222) than that in male cases (0.1818) (Z=3.49, p<0.05). As for association studies, significant association between bipolar disorder and MAOB gene was detected. For the 180 bp allele of MAOB(GT)n, the relative risk (RR) of biploar versus normal control was 2.58 (p<0.05), and the RR of female bipolar disorder versus female normal control was 3.63 (p<0. 05). For the 205 bp allele of MAOB(TG)n, the RR of female bipolar disorder versus female normal control was 2.29 (p<0.05). Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:12-14, 2000. 相似文献
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Association of a functional polymorphism of the monoamine oxidase A gene promoter with personality and psychiatric symptoms 总被引:1,自引:0,他引:1
Jorm AF Henderson AS Jacomb PA Christensen H Korten AE Rodgers B Tan X Easteal S 《Psychiatric genetics》2000,10(2):87-90
A functional polymorphism in the promoter of the monoamine oxidase gene has recently been described by Sabol et al. This polymorphism is a strong candidate for associations with personality traits and psychiatric symptoms. We report relevant data from a general population sample of 850 Caucasian Australians. We found no associations with anxiety and depression symptoms, with personality traits that predispose to anxiety (neuroticism, behavioral inhibition, negative affect) or to a personality trait related to antisocial behavior (psychoticism). 相似文献
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No association between a TPH2 promoter polymorphism and mood disorders or monoamine turnover 总被引:1,自引:0,他引:1
Mann JJ Currier D Murphy L Huang YY Galfalvy H Brent D Greenhill L Oquendo M 《Journal of affective disorders》2008,106(1-2):117-121
BACKGROUND: Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in serotonin synthesis. TPH2 is a recently discovered isoform that is expressed predominantly in serotonin neurons. Associations are reported of TPH2 polymorphisms with MDD, bipolar disorder and suicidal behavior. This study examines a single nucleotide polymorphism in the putative promoter region of the TPH2 gene. METHODS: One hundred nine bipolar, 324 major depressive disorder, and 130 healthy volunteers were genotyped for the rs4131347 (-C8347G) promoter SNP. Association was assessed with diagnosis, suicide attempt status, severity of psychopathology and cerebrospinal fluid monoamine metabolite levels of 5-HIAA, HVA, and MHPG. General linear models and logistic regression tested the effect of genotype*childhood abuse interactions on psychopathology severity and suicide attempt. RESULTS: There was no association between genotype and either mood disorder, suicide attempt status, psychopathology severity or CSF monoamine metabolite levels. CONCLUSIONS: No association was detected between the rs4131347 (-C8347G) SNP in the promoter region of the TPH2 gene and mood disorders, suicidal behavior or monoamine function. 相似文献
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Cohen IL Liu X Schutz C White BN Jenkins EC Brown WT Holden JJ 《Clinical genetics》2003,64(3):190-197
A functional polymorphism (the upstream variable-number tandem repeat region, or uVNTR) in the monoamine oxidase A (MAOA) promoter region has been reported to be associated with behavioral abnormalities as well as increased serotonergic responsivity. We examined the relation between MAOA-uVNTR alleles and the phenotypic expression of autism in 41 males younger than 12.6 years of age. Children with the low-activity MAOA allele had both lower intelligence quotients (IQ) and more severe autistic behavior than children with the high-activity allele. In follow-up testing of 34 of the males at the 1-year time-point, those with the low-activity allele showed a worsening in IQ but no change in the severity of their autistic behavior. We conclude that functional MAOA-uVNTR alleles may act as a genetic modifier of the severity of autism in males. 相似文献
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No evidence of an association between a functional monoamine oxidase a gene polymorphism and completed suicides 总被引:5,自引:0,他引:5
Ono H Shirakawa O Nishiguchi N Nishimura A Nushida H Ueno Y Maeda K 《American journal of medical genetics》2002,114(3):340-342
Monoamine oxidase A (MAOA) has been implicated in the control of aggression and/or impulsivity in humans and been involved in suicide. This gene has a functional polymorphism in which there is a variable number tandem repeat (VNTR) in the upstream region (MAOA-uVNTR). We hypothesized that MAOA dysfunction due to this polymorphism was associated with suicide genetically through the disinhibition of aggression and/or impulsivity. We performed an association study between completed suicides and the MAOA-uVNTR polymorphism. No significant difference in genotype distribution or allele frequencies was found between completed suicides and comparison groups either in males or females. These results show no evidence of an association between the MAOA-uVNTR polymorphism and completed suicides and suggest that MAOA is not involved in the susceptibility to suicide. 相似文献
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Hakamata Y Takahashi N Ishihara R Saito S Ozaki N Honjo S Ono Y Inada T 《Neuroscience letters》2005,389(3):121-123
Monoamine oxidase A (MAO-A) is an enzyme involved in the metabolism of monoamine neurotransmitters such as dopamine, serotonin, and noradrenaline in the brain. Previous studies have demonstrated a significant association between MAO-A gene polymorphism and personality traits in males. The purpose of the present study was to examine this association in females. The subjects were 219 healthy Japanese females. We genotyped a variable number of tandem repeats located upstream of the MAO-A gene. Personality traits were assessed using the Temperament and Character Inventory (TCI). There was no association between any personality trait and MAO-A genotype. The present results do not support the hypothesis that MAO-A gene polymorphism is related to certain personality traits in females. 相似文献
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Yuji Morimoto Nobuhiro Murayama Akira Kuwano Ikuko Kondo Yoriaki Yamashita Yoshikuni Mizuno 《American journal of medical genetics. Part A》1995,60(6):570-572
The polymorphic allele of the monoamine oxidase B (MAO-B) gene detected by polymerase chain reaction (PCR) and single-stranded conformation polymorphism (SSCP) was associated with Parkinson's disease (PD) in Caucasians. We characterized this polymorphic allele, allele 1, of the MAO-B gene using direct sequencing of PCR products. A single DNA substitution (G-A), resulting gain of Mae III restriction site was detected in intron 13 of the MAO-B gene. The allele associated with PD in Caucasians was twice as frequent as in healthy Japanese, but the association of the allele of the MAO-B gene was not observed in Japanese patients with PD. © 1995 Wiley-Liss, Inc. 相似文献
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Burkart KM Barton SJ Holloway JW Yang IA Cakebread JA Cruikshank W Little F Jin X Farrer LA Clough JB Keith TP Holgate S Center DM O'Connor GT 《The Journal of allergy and clinical immunology》2006,117(1):86-91
BACKGROUND: IL-16, a multifunctional cytokine with increased expression in the airways of asthmatic subjects, inhibits allergic airway inflammation in animal models. A T-->C single nucleotide polymorphism (SNP) at the -295 position in the promoter region of the IL16 gene has been described. OBJECTIVE: We sought to examine the functional significance of this promoter SNP and its relationship to asthma. METHODS: We examined the effect of the -295 SNP on promoter activity in cell-line (HBE4-E6/E7) transfection experiments. We investigated the association of the IL16 -295 genotype with asthma among 341 affected sib-pair white families and 184 unrelated nonasthmatic control subjects. We analyzed the association between the IL16 genotype and asthma using family-based association test and case-control analyses. RESULTS: In in vitro transfection experiments the T allele in the -295 position was associated with substantially reduced promoter activity compared with the C allele. In the family study the more common T allele at the -295 position was significantly associated with all asthma phenotypes (P = .002 to P = .015). In the case-control analysis asthmatic subjects were more likely than unrelated nonasthmatic control subjects to have the -295 TT genotype, but this did not reach statistical significance (odds ratio, 1.36; 95% CI, 0.92-2.02). CONCLUSIONS: The T allele at the -295 position in the IL16 promoter region is associated with reduced promoter activity relative to the C allele and with asthma in this white population. Further investigation is needed to delineate the mechanisms underlying these findings and the relationship of the IL16 -295 genotype to asthma in other populations. 相似文献
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Paola Costa Harvey Checkoway Drew Levy Terri Smith-Weller Gary M. Franklin Phillip D. Swanson Lucio G. Costa 《American journal of medical genetics. Part A》1997,74(2):154-156
Monoamine oxidase B (MAO-B) is an enzyme that has relevance for Parkinson disease (PD) because of its roles in catabolizing dopamine and potentially activating exogenous neurotoxicants. A polymorphism of the gene encoding MAO-B has been identified as a single base change (A or G) in intron 13 of the X chromosome. The A allele was previously associated with an approximately twofold risk of PD. The present study compared A and G allele frequencies between newly diagnosed idiopathic PD cases and a control group free of neurodegenerative diseases. All study subjects were Caucasian. Cases were 37 men and 25 women, age 37–80 years; controls were 50 men and 29 women, age 45–82 years. MAO-B genotype was determined by the allele-specific polymerase chain reaction on DNA extracted from peripheral lymphocytes. In complete contrast to previous studies, elevated risks were detected with the G allele. The age-adjusted odds ratio for the G allele in males was 1.87 ((95% confidence interval) 0.78–4.47). Among females the age-adjusted odds ratios were 5.00 ((95% confidence interval) 1.13–22.1) for the GA genotype and 5.60 ((95% confidence interval) 1.01–30.9) for the GG genotype. These findings, although of limited statistical precision, suggest that the G allele of this MAO-B polymorphism may relate to PD risk. Am. J. Med. Genet. 74:154–156, 1997. © 1997 Wiley-Liss, Inc. 相似文献
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Erik G J?nsson Sven Cichon Johannes Schumacher Rami Abou Jamra Thomas G Schulze Monica Deschner Kaj Forslund H?kan Hall Peter Propping Piotr M Czerski Monica Dmitrak-Weglarz Pawel Kapelski Martin Driessen Wolfgang Maier Joanna Hauser Marcella Rietschel Markus M N?then 《American journal of medical genetics. Part B, Neuropsychiatric genetics》2006,(1):71-75
A functional promoter polymorphism (-116C/G) of the X-box binding protein 1 gene (XBP1) gene was reported to be associated with schizophrenia in Asian subjects. In a replication attempt, three European case-control samples comprising 2,182 German, Polish, and Swedish subjects, were genotyped for the XBP1 -116C/G polymorphism. Allele and genotype frequencies were compared between schizophrenic patients and control subjects. There were no significant case-control differences in any of the three samples, although in a meta-analysis with previous results comprising 3,612 subjects there was a borderline association between the -116G-containing genotypes and schizophrenia. We conclude that the functional XBP1 gene polymorphism is not of major importance to schizophrenia in the European populations investigated. It cannot be excluded, however, that the XBP1 polymorphism is involved in schizophrenia in other populations or adds minor susceptibility to the disorder. 相似文献
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Family-based and population study of a functional promoter-region monoamine oxidase A polymorphism in autism: possible association with IQ 总被引:2,自引:0,他引:2
Yirmiya N Pilowsky T Tidhar S Nemanov L Altmark L Ebstein RP 《American journal of medical genetics》2002,114(3):284-287
Although the etiology of autism remains to be elucidated, genetic elements significantly contribute to this disorder, and genes on the X chromosome are of special interest because there is a 4:1 predominance of male probands in autism. In the current study, we therefore examined, using the robust transmission disequilibrium test (TDT), possible preferential transmission of variants of a functional monoamine oxidase A (MAO A) promoter region polymorphism for linkage to autism. In the 49 families examined (33 families with one proband and 15 families with two affected siblings), we did not find preferential transmission of MAO A from 33 heterozygous mothers to affected child (TDT chi-square = 0.29, NS). Nor was any significant difference in MAO A allele frequency observed between 43 male autism subjects versus a group of 108 non-autism control subjects (chi-square = 1.23, P = 0.27, NS). However, a trend was observed for an association between IQ in the probands and the MAO A genotype that just attained significance (F = 3.5, P = 0.046, N = 28) in the small group of autism subjects recruited from families with two affected siblings. 相似文献
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Chen-Jee Hong Shih-Jen Tsai Chih-Ya Cheng Wen-Yu Liao Hsiu-Li Song Hao-Che Lai 《American journal of medical genetics. Part A》1999,88(6):601-602
The serotonergic system is implicated in the etiology of mood disorders. Among those most recently discovered serotonin receptors, the relative abundance of serotonin type 6 receptor (5-HT6) in the limbic area and the high affinity of some antidepressants to 5-HT6 receptors suggest that this receptor might be involved in the pathogenesis of mood disorders. In a population-based association study, we tested the hypothesis that the allelic variant (C267T) of the human 5-HT6 gene confers susceptibility to mood disorders. We genotyped the 5-HT6 receptor in 139 patients with mood disorders and 147 controls. The results demonstrated that there were no significant differences in genotype or allele frequencies between controls and all patients, or between controls and patients with bipolar disorders or major depression, separately. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:601–602, 1999. © 1999 Wiley-Liss, Inc. 相似文献