Characterization of a highly polymorphic region near the first exon of the human MAOA gene containing a GT dinucleotide and a novel VNTR motif

Hinds, Heather L.; Hendriks, Rudolf W.; Craig, Ian W.; Chen, Zhengyi

doi:10.1016/0888-7543(92)90181-q

Cited by 65 publications

(39 citation statements)

References 8 publications

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“…Only three (A, B, and C) of the five different alleles described by Hinds et al 19 were found in our sample. Genotype frequencies were distributed according to Hardy-Weinberg equilibrium n refers to the number of total alleles at MAO-A locus ('n' in males, '2n' in females).…”

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confidence: 63%

“…DNA was amplified using polymerase chain reaction (PCR). For the MAOA gene we studied a VNTR marker located in the first intron of the gene; PCR amplification was made using the primers and conditions described by Hinds et al 19 For the MAOB gene we analyzed a dinucleotide sequence (GT)n in the second intron of the gene. 21 Amplified products obtained by PCR were resolved by electrophoresis in denaturing polyacrylamide gels and detected by silver staining.…”

Section: Dna Amplification and Genotypingmentioning

confidence: 99%

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Pathological gambling and DNA polymorphic markers at MAO-A and MAO-B genes

et al. 2000

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This study was conducted to detect a possible association of MAOA and/or MAOB genes with pathological gambling (PG). DNA polymorphisms in MAOA and MAOB genes were screened by molecular analysis in 68 individuals (47 males and 21 females) meeting ICD-10 and DSM-IV criteria for pathological gambling and 68 healthy comparison controls matched for age and sex. There were no significant differences between pathological gamblers and healthy volunteers in overall allele distribution at the MAOA gene polymorphism. However there was a significant association between allele distribution and the subgroup of severe male gamblers (n = 31) compared to the males in the group of healthy volunteers ( 2 = 5246; df = 1; P Ͻ 0.05 [Bonferroni corrected]). No association was found between the MAOB polymorphic marker and PG. Allele variants at the MAOA, but not the MAOB gene may be a genetic liability factor in PG, at least in severe male gamblers. Molecular Psychiatry (2000) 5, 105-109.Pathological gambling is an impulse control disorder and it has also been proposed as a model of addiction without substance. 1 As defined by DSM-IV its essential feature is a persistent and recurrent maladaptive gambling behaviour. It is a progressive, chronic and highly disabling disorder that is poorly understood and often underdiagnosed despite affecting 1-3% of the adult population. 2 At present, little is known about the biological correlates of pathological gambling. A growing literature suggests the involvement of genetic factors in behavioral disorders related to pathological gambling such as alcoholism, substance abuse, attention-deficithyperactivity disorder, and smoking. 3 An increased incidence of about 20% of pathological gambling in first-degree relatives within clinical samples of pathological gamblers has been reported 4,5 and it has led to consideration of the possible role of a genetic component in the development of this disorder. Moreover, there is evidence for genetic influence derived from a large twin study performed on 3359 twin pairs in United States. This study revealed that inherited factors explained 62% of the diagnosis of pathological gambling disorder. 6 Recently, a positive association has been reported between pathological gambling and DNA polymorphism at the D2 and D4 receptor genes. 7,8 Monoamine oxidases A (MAOA) and B (MAOB) play a critical role in the degradation of several neurotransmitters which could be involved in the pathogenesis of pathological gambling. Decreased platelet MAOB activity has been reported in pathological gambling 9,10 and other impulse control disorders. 11,12 Although MAOA activity has never been studied in pathological gambling, previous research suggests that abnormal MAOA activity may play a role in the pathophysiology of disorders with impaired impulse control. 13 Decreased MAOA activity was associated with impulsive behaviors in several affected males from a large Dutch family with a mutation in that locus. 14 Differences in MAOA activity have been associated with specific alleles of th...

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confidence: 63%

Section: Dna Amplification and Genotypingmentioning

confidence: 99%

Pathological gambling and DNA polymorphic markers at MAO-A and MAO-B genes

et al. 2000

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“…Several polymorphisms have previously been described: a GT dinucleotide repeat polymorphism near exon 2 (MAOA-CA) (Black et al, 1991), a polymorphic region near exon 1 containing a GT microsatellite directly adjacent to an imperfectly duplicated 23-bp repeat motif (MAOA-VNTR) (Hinds et al, 1992), two functional restriction fragment length polymorphisms (Fnu4HI and EcoRV) (Lim et al, 1994), and the MAOA gene-linked polymorphic region (MAOA-LPR, MAOA-uVNTR), a functional 30-bp repetitive sequence located in the gene's transcriptional control region approximately 1.2 kb upstream of the ATG codon (Sabol et al, 1998;Deckert et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Cluster B Personality Disorders are Associated with Allelic Variation of Monoamine Oxidase A Activity

Jacob

Müller

Schmidt

et al. 2005

Neuropsychopharmacol

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Genetic variants of the monoamine oxidase A (MAOA) have been associated with aggression-, anxiety-, and addiction-related behavior in several nonclinical and clinical populations. Here, we investigated the influence of allelic variation of MAOA activity on aggressionrelated personality traits and disease risk in patients with personality disorders. Personality disorders were diagnosed with the Structured Clinical Interview of DSM-IV and were allocated to cluster A, B, and C. Personality features were assessed by the revised NEO Personality Inventory and the Tridimensional Personality Questionnaire. The genotype of the MAOA gene-linked polymorphic region (MAOA-LPR) was determined in 566 patients with personality disorders and in 281 healthy controls. MAOA genotype was significantly associated with cluster B personality disorders (w 2 ¼ 7.77, p ¼ 0.005, df ¼ 1) but not with cluster C personality disorders. In total, 26.0% of cluster B patients were hemi-or homozygous for the low-activity variant of the MAOA genotype, compared to 16.4% in the control group. Associations between MAOA variants and personality domains related to impulsivity and aggressiveness were inconsistent. Our findings further support the notion that allelic variation of MAOA activity contributes modestly to the balance of hyper-(impulsiveaggressive) and hyporeactive (anxious-depressive) traits.

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“…7 Finally, transgenic mice lacking the MAO A gene are characterized by aggressive behavior and higher brain levels of monoaminergic neurotransmitters. 8 A number of polymorphic sites have been described for these two enzymes, 9,10 including a dinucleotide repeat in MAO A, 11,12 but the most noteworthy is a repeat region in the MAO A promoter region. 13 This polymorphism is located 1.2 kb upstream of the MAOA coding sequences, consists of a 30-bp repeated sequence present in 2 (291 bp), 3 (321 bp), 3.5 (336 bp), 4 (351 bp), or 5 (381 bp) copies.…”

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Family-based and association studies of monoamine oxidase A and attention deficit hyperactivity disorder (ADHD): preferential transmission of the long promoter-region repeat and its association with impaired performance on a continuous performance test (TOVA)

et al. 2002

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Monoamine oxidase A (MAO A) is located on the X chromosome and metabolizes biogenic amines including dopamine, norepinephrine and serotonin. A functional promoter-region polymorphism of this gene has been described that has been studied in a number of mental illnesses but not in attention deficit hyperactivity disorder (ADHD). In the current study, we examined the MAO A promoter-region polymorphism initially in 133 triads and observed preferential transmission of the long alleles from 74 heterozygote mothers to ADHD probands ( 2 = 4.37, P = 0.036, df = 1). We also examined the role of this polymorphism in a computerized continuous performance test, the TOVA. Significant differences were observed on errors of commission ( 2 = 7.021, P = 0.008) and patients carrying the long MAO A allele made significantly more such errors. Errors of commission are a measure of impulsivity. However, following Ritalin (methylphenidate) administration the association between this polymorphism and errors of commission was markedly attenuated and no longer significant at the P Ͻ 0.05 level. We also analyzed the provisional association by the case-control design. A significant difference in allele frequency was observed between 110 male probands vs 202 male controls (Pearson 2 = 7.94, P = 0.047). Similarly results were obtained when 19 female probands were compared to female controls (genotype 2 = 21.28; P = 0.0032, 3 df and allele 2 = 30.88, P = 0.0007, 2 df). All three complementary approaches employed (family-based, case-control and quantitative trait design) suggest a role for the MAO A promoter-region polymorphism in conferring risk for ADHD in our patient population.

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Characterization of a highly polymorphic region near the first exon of the human MAOA gene containing a GT dinucleotide and a novel VNTR motif

Cited by 65 publications

References 8 publications

Pathological gambling and DNA polymorphic markers at MAO-A and MAO-B genes

Pathological gambling and DNA polymorphic markers at MAO-A and MAO-B genes

Cluster B Personality Disorders are Associated with Allelic Variation of Monoamine Oxidase A Activity

Family-based and association studies of monoamine oxidase A and attention deficit hyperactivity disorder (ADHD): preferential transmission of the long promoter-region repeat and its association with impaired performance on a continuous performance test (TOVA)

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