MAOB Polymorphisms Research Articles

The Relationship Between COMT and MAO-B Gene Polymorphisms with Levodopa in Parkinson’s Disease Patients; A Review

Parkinson's disease is a degenerative nervous system disorder caused by the death of dopamine-producing cells in the substantia nigra. Dopaminergic treatment could alleviate motor symptoms for a period. One of the effective dopaminergic medications for symptomatic relief was Levodopa and dopamine agonists. Clinically, Levodopa was always combined with Dopa Decarboxylase (DDC) inhibitors, which redirected Levodopa metabolism towards the COMT pathway, increasing its bioavailability in the central nervous system. The purpose of this article was to investigate the relationship between COMT and MAO-B gene polymorphisms and Levodopa in Parkinson's disease patients, starting by gathering literature on the association between COMT and MAO-B polymorphisms and Levodopa in Parkinson's disease patients using various databases. Reviewed literature revealed that the most frequent polymorphism in the COMT gene was rs4680. Some polymorphisms significantly impacted the treatment of Parkinson's disease patients. However, despite efforts to identify genetic factors influencing the risk of side effects or treatment ineffectiveness, the role of pharmacogenetics in Parkinson's disease has not been fully explored and lacks consistent clinical recommendations. Further research was needed to tailor treatment to individual polymorphisms so that pharmacogenomic approaches could be applied more consistently

MAO-B Polymorphism Associated with Progression in a Chinese Parkinson's Disease Cohort but Not in the PPMI Cohort.

Introduction Genetic factors play an important role in Parkinson's disease (PD) risk. However, the genetic contribution to progression in Chinese PD patients has rarely been studied. This study investigated genetic associations with progression based on 30 PD risk loci common in a longitudinal cohort of Chinese PD patients and the Parkinson's Progression Markers Initiative (PPMI) cohort. Methods PD patients from the true world (TW) Chinese PD longitudinal cohort and the PPMI cohort with demographic information and assessment scales were assessed. A panel containing 30 PD risk single nucleotide polymorphisms was tested. Progression rates of each scale were derived from random-effect slope values of mixed-effects regression models. Progression rates of multiple assessments were combined by using principal component analysis (PCA) to derive scores for composite, motor, and nonmotor progression. The association of genetic polymorphism and separate scales or PCA progression was analysed via linear regression. Results In the Chinese PD cohort, MAOB rs1799836 was associated with progression based on the Montreal Cognitive Assessment, the top 3 principal components (PCs) of nonmotor PCA and PC1 of the composite PCA. In the PPMI cohort, both MDS-Unified Parkinson's Disease Rating Scale II and motor PC1 progression were associated with RIT2 rs12456492. The PARK16 haplotype was associated with Geriatric Depression Scale and the State-Trait Anxiety Inventory for Adults progression, and the SNCA haplotype was associated with the Hoehn-Yahr staging progression and motor PC1 progression. Ethnicity-stratified analysis showed that the association between MAOB rs1799836 and PD progression may be specific to Asian or Chinese patients. Conclusion MAOB rs1799836 was associated with the progression of nonmotor symptoms, especially cognitive impairment, and the composite progression of motor and nonmotor symptoms within our Chinese PD cohort. The RIT2 rs12456492 and SNCA haplotypes were associated with motor function decline, and the PARK16 haplotype was associated with progression in mood in the PPMI cohort.

Functional MAOB Gene Intron 13 Polymorphism Predicts Dyskinesia in Parkinson's Disease.

Identification of individual risk factors for motor complications in Parkinson's disease (PD) can help to guide personalised medical treatment, particularly since treatment options are still limited. To determine whether common functional gene polymorphisms in the dopamine metabolism predict the onset of motor complications in PD, we performed a retrospective, observer-blinded follow-up study of 30 PD patients who underwent genotyping of dopa-decarboxylase (DDC; rs921451), monoamine oxidase B (MAOB; rs1799836), catechol-O-methyltransferase (COMT; rs4680), and dopamine transporter (DAT; variable number tandem repeat) polymorphisms. Onset of wearing-off and dyskinesias was determined by blinded clinical assessments. Predictive values of genotypes for motor complications were evaluated using Cox proportional hazard models. During a median follow-up time of 11.6 years, 23 (77%) of 30 PD patients developed wearing-off, 16 (53%) dyskinesias, and 23 (77%) any motor complication. The MAOB (rs1799836) polymorphism predicted development of dyskinesias with MAOBCC/(C)/CT genotypes (resulting in low/intermediate brain enzyme activity) being associated with lower hazard ratios (unadjusted HR [95% CI]: 0.264 [0.089–0.787]; p=0.012; adjusted HR [95% CI]: 0.142 [0.039–0.520]; p=0.003) than MAOBTT/(T) genotypes (resulting in high brain enzyme activity). DDC (rs921451), COMT (rs4680), and DAT (VNTR) polymorphisms were not predictive of motor complications. Together, the MAOB (rs1799836) polymorphism predicts the development of dyskinesias in PD patients. Our results need confirmation in larger cohorts. If confirmed, individual assessment of this polymorphism might be helpful for early risk stratification and could comprise a step towards patient-tailored therapeutic strategies to prevent or delay motor complications in the course of PD.

Functional monoamine oxidase B gene intron 13 polymorphism predicts putaminal dopamine turnover in de novo Parkinson's disease.

The objective of this study was to evaluate the effects of common functional polymorphisms in genes involved in dopamine metabolism on striatal dopamine turnover in de novo Parkinson's disease (PD). This was an observer-blinded cohort study investigating effects of common functional polymorphisms in dopa decarboxylase (DDC, rs921451), monoamine oxidase B (MAOB; rs1799836), catechol-O-methyltransferase (COMT, rs4680), and dopamine transporter/solute carrier family 6 member 3 (DAT/SLC6A3, variable number tandem repeats) genes on 18 F-fluorodopa uptake and an effective distribution volume ratio (inverse of dopamine turnover) measured by 18 F-fluorodopa PET in 28 untreated PD patients. Patients carrying the MAOBCC/(C)/CT genotype (low/intermediate enzyme activity) had a lower dopamine turnover in the putamen (higher mean effective distribution volume ratio) when compared with patients with MAOBTT/(T) genotype (high enzyme activity). Striatal PET measures were not different between variants in the remaining genes. The MAOB (rs1799836) polymorphism predicts putaminal dopamine turnover in early PD with the MAOBTT allele linked to high enzyme activity leading to higher intrinsic dopamine turnover, which has been demonstrated to constitute a risk factor for motor complications. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Maoa and Maob polymorphisms and personality traits in suicide attempters and healthy controls: a preliminary study

Serotonergic neurotransmission dysfunctions have been well documented in patients with suicidal behaviour. We investigated monoamine oxidase A (MAOA: rs2064070, rs6323, rs909525) and B (MAOB: rs1799836, rs2311013, rs2205655) genetic modulation of personality traits (Temperament and Character Inventory, TCI) as endophenotype for suicidal behaviour. 108 suicide attempters and 286 healthy controls of German origin were screened. Among females, allelic analyses revealed associations between MAOA rs6323 A allele and higher Harm Avoidance in suicide attempters and MAOB rs2205655 A allele and higher Cooperativeness scores in healthy controls. Among males, MAOA rs909525 A allele was associated with higher Reward Dependence in suicide attempters. Multivariate analyses controlling for age and educational level mainly confirmed results. Case-control analyses in this subsample do not differ from our previously reported one. Despite of the small sample size, a possible involvement of these genes in the modulation of personality traits closely related to suicidal behaviour cannot be excluded.

Genetic Variants of Neurotransmitter‐Related Genes and miRNAs in Egyptian Autistic Patients

Autism is a neurodevelopmental disorder with indisputable evidence for a genetic component. This work studied the association of autism with genetic variations in neurotransmitter-related genes, including MAOA uVNTR, MAOB rs1799836, and DRD2 TaqI A in 53 autistic patients and 30 healthy individuals. The study also analyzed sequence variations of miR-431 and miR-21. MAOA uVNTR was genotyped by PCR, MAOB and DRD2 polymorphisms were analyzed by PCR-based RFLP, and miR-431 and miR-21 were sequenced. Low expressing allele of MAOA uVNTR was frequently higher in female patients compared to that in controls (OR = 2.25). MAOB G allele frequency was more significantly increased in autistic patients than in controls (P < 0.001 for both males and females). DRD2 A1+ genotype increased autism risk (OR = 5.1). Severity of autism tends to be slightly affected by MAOA/B genotype. Plasma MAOB activity was significantly reduced in G than in A allele carrying males. There was no significant difference in patients and maternal plasma MAOA/B activity compared to controls. Neither mutations nor SNPs in miR-431 and miR-21 were found among studied patients. This study threw light on some neurotransmitter-related genes suggesting their potential role in Autism pathogenesis that warrants further studies and much consideration.

MAOA and MAOB polymorphisms and anger-related traits in suicidal participants and controls

MAOA and, to a lesser extent, MAOB polymorphisms have been related to aggression traits and suicidality. We aimed to investigate the role of MAOA and MAOB in suicidal versus non-suicidal participants and interactions between genetic variation and suicidal status on aggression and anger-related traits. The sample was composed of three groups: one group of suicide attempters (n = 171, males 35.1 %), one group of suicide completers (n = 90, males 57.8 %) and a healthy control group (n = 317, males 43.8 %). We examined the following markers: MAOA rs909525, rs6323, and rs2064070, and MAOB rs1799836. Anger traits were measured with the state-trait anger expression inventory (STAXI) and aggression traits with the questionnaire for measuring factors of aggression (FAF). Associations were separately examined for males and females. Variation in the three MAOA variants was associated with higher levels of anger expressed outwards (STAXI "anger-out" subscale) in male suicidal patients compared to controls (p < 0.001). In females, the C allele of rs6323 showed higher scores on the same subscale ("anger out") (p = 0.002). Allele frequencies of the MAOA rs909525 were associated with suicidality (p < 0.007). Our findings show an association between genetic variation in three polymorphisms of the MAOA and anger traits in suicidal males and one replication for the functional variant rs6323 in females. This relationship was stronger than a direct genetic association with suicide status. Future studies incorporating endophenotypic measures of anger and aggression in suicidal participants are warranted.

Original article Association of monoamine oxidase B and catechol-O-methyltransferase polymorphisms with sporadic Parkinson’s disease in an Iranian population

Genetic polymorphisms have been shown to be involved in dopaminergic neurotransmission. This may influence susceptibility to Parkinson's disease (PD). We performed a case-control study of the association between PD susceptibility and a genetic polymorphism of MAOB and COMT, both separately and in combination, in Iranians. The study enrolled 103 Iranian patients with PD and 70 healthy individuals. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) methods were used for genotyping. Our data indicated that the MAOB genotype frequencies in PD patients did not differ significantly from the control group. However, the frequency of MAOB GG genotype was significantly lower in female patients. It has been shown that the distribution of MAOB allele A was slightly higher in PD patients. No statistically significant differences were found in the COMT allele and genotype distribution in PD patients in comparison to the controls. The combined haplotype of the MAOB A, A/A and COMT LL genotype showed a slight increase in the risk of PD in female patients in this Iranian population. The data may suggest that the MAOB and COMT genetic polymorphisms do not play any role in the pathogenesis of PD in Iranians. In addition, the combined haplotype of MAOB and COMT genes did not significantly affect the susceptibility to PD. Future studies involving larger control and case populations will undoubtedly lead to a more thorough understanding of the role of the polymorphisms involved in the dopamine pathway in PD.

Association study of monoamine oxidase A/B genes and schizophrenia in Han Chinese

BackgroundMonoamine oxidases (MAOs) catalyze the metabolism of dopaminergic neurotransmitters. Polymorphisms of isoforms MAOA and MAOB have been implicated in the etiology of mental disorders such as schizophrenia. Association studies detected these polymorphisms in several populations, however the data have not been conclusive to date. Here, we investigated the association of MAOA and MAOB polymorphisms with schizophrenia in a Han Chinese population.MethodsTwo functional single nucleotide polymorphisms (SNPs), rs6323 of MAOA and rs1799836 of MAOB, were selected for association analysis in 537 unrelated schizophrenia patients and 536 healthy controls. Single-locus and Haplotype associations were calculated.ResultsNo differences were found in the allelic distribution of rs6323. The G allele of rs1799836 was identified as a risk factor in the development of schizophrenia (P = 0.00001). The risk haplotype rs6323T-rs1799836G was associated with schizophrenia in female patients (P = 0.0002), but the frequency difference was not significant among male groups.ConclusionsOur results suggest that MAOB is a susceptibility gene for schizophrenia. In contrast, no significant associations were observed for the MAOA functional polymorphism with schizophrenia in Han Chinese. These data support further investigation of the role of MAO genes in schizophrenia.

Negative emotionality: monoamine oxidase B gene variants modulate personality traits in healthy humans.

Monoamine oxidase A and B (MAOA and MAOB) appear to be involved in the pathogenesis of Major Depression, and vulnerability of Major Depression is associated with personality traits relating to positive and negative affect. This study aimed to investigate associations between MAOA and MAOB polymorphisms and personality traits of positive and negative emotionality in healthy volunteers, to elucidate mechanisms underlying personality and the risk for depression. Healthy Caucasian volunteers (N = 150) completed the Multiphasic Personality Questionnaire (MPQ), which includes independent superfactors of Positive Emotionality and Negative Emotionality. Participants were genotyped for 8 MAOA and 12 MAOB single nucleotide polymorphisms (SNPs). Association analyses for both SNPs and haplotypes were performed using the permutation approach implemented in PLINK. Negative Emotionality was significantly associated with the two highly linked MAOB polymorphisms rs10521432 and rs6651806 (p < 0.002). Findings were extended in haplotype analyses. For MAOB the 4-SNP haplotype GACG formed from rs1799836, rs10521432, rs6651806 and rs590551 was significantly related to lower Negative Emotionality scores (p < 0.002). MAOA was not related to personality in this study. Our finding provides the first evidence that MAOB polymorphisms influence levels of negative emotionality in healthy human volunteers. If confirmed, these results could lead to a better understanding of personality traits and inter-individual susceptibility developing psychiatric disorders such as major depression.

Association study of monoamine oxidase and catechol-O-methyltransferase genes with smoking behavior

The genes of catalytic enzymes of dopamine, including monoamine oxidase (MAOA and MAOB) and catechol-O-methyltransferase (COMT), have been major candidates for genes that affect smoking behavior. In this study, we investigated the relationship between smoking behavior and four polymorphisms of these genes, the MAOA variable number tandem repeat polymorphism, the MAOA 1460 T/C polymorphism, the MAOB intron 13 G/A polymorphism, and the COMT Val158Met polymorphism. The association between the MAOB polymorphism and personality traits was also explored. The polymorphisms were genotyped in 451 healthy Japanese volunteers. Data on smoking habits were obtained from structured interviews. In addition to testing the association between each polymorphism and smoking status, epistatic and additive effects between two polymorphisms were also investigated. A significant association was observed between the COMT Val158Met polymorphism and smoking status. Male participants with the Val/Val genotype had a significantly higher risk of heavy smoking compared with those with other genotypes, although no significant association was observed in female participants. No evidence was obtained for an association between the MAO genes and smoking behavior, including epistatic or additive effects. No significant association was observed between the MAOB polymorphism and personality traits. This study may suggest a role of the COMT Val158Met polymorphism in smoking behavior in Japanese individuals.

Which genotype of MAO gene that the patients have are likely to be most susceptible to the symptoms of fibromyalgia?

The objective of this study was to analyze the genotype distributions and allele frequencies for the MAO-A and MAO-B polymorphism of the MAO gene among the patients with fibromyalgia syndrome (FS). One hundred and seven fibromyalgia patients and 90 unrelated healthy subjects were included into the study. Genomic DNA of 107 FS patients and 90 healthy control subjects were analyzed by polymerase chain reaction. Polymorphism of the MAO gene was: 1-1, 1-3, 3-3, 3-4. The "allele 3" had a 2.7 to 4.8-fold increased transcription activity than the "allele 1". The frequencies of the genotypes of the patients with FS and healthy controls were compared. Although no significant difference was found in genotypes of patients and controls (P = 0.0559), it is likely that "allele 3" could be a more riskful factor for FS than "allele 1" (P = 0.033). Fibromyalgia impact questionnaire was administered to FS group as well as control group. One of our findings is that, the patients whose genotype 3-3 may be mostly affected by the symptoms of FS. In conclusion, it seems plausible to say that MAOA-dependent metabolism of the biological amines may be partly related to high-activated MAO-A, allele 3, in the occurrence of FS among Turkish population.

X-APL: An Improved Family-Based Test of Association in the Presence of Linkage for the X Chromosome

Family-based association methods have been developed primarily for autosomal markers. The X-linked sibling transmission/disequilibrium test (XS-TDT) and the reconstruction-combined TDT for X-chromosome markers (XRC-TDT) are the first association-based methods for testing markers on the X chromosome in family data sets. These are valid tests of association in family triads or discordant sib pairs but are not theoretically valid in multiplex families when linkage is present. Recently, XPDT and XMCPDT, modified versions of the pedigree disequilibrium test (PDT), were proposed. Like the PDT, XPDT compares genotype transmissions from parents to affected offspring or genotypes of discordant siblings; however, the XPDT can have low power if there are many missing parental genotypes. XMCPDT uses a Monte Carlo sampling approach to infer missing parental genotypes on the basis of true or estimated population allele frequencies. Although the XMCPDT was shown to be more powerful than the XPDT, variability in the statistic due to the use of an estimate of allele frequency is not properly accounted for. Here, we present a novel family-based test of association, X-APL, a modification of the test for association in the presence of linkage (APL) test. Like the APL, X-APL can use singleton or multiplex families and properly infers missing parental genotypes in linkage regions by considering identity-by-descent parameters for affected siblings. Sampling variability of parameter estimates is accounted for through a bootstrap procedure. X-APL can test individual marker loci or X-chromosome haplotypes. To allow for different penetrances in males and females, separate sex-specific tests are provided. Using simulated data, we demonstrated validity and showed that the X-APL is more powerful than alternative tests. To show its utility and to discuss interpretation in real-data analysis, we also applied the X-APL to candidate-gene data in a sample of families with Parkinson disease.

Family‐based case–control study of MAOA and MAOB polymorphisms in Parkinson disease

Monoamine oxidase (MAO) is an enzyme regulating metabolism of neurotransmitters such as dopamine. Two distinct forms of enzyme, encoded by genes MAOA and MAOB located on the X chromosome, have been considered as possible factors in the pathogenesis of Parkinson disease (PD). Previous association studies of PD and MAO genes reported inconsistent results. In this study, we used a large family-based data set to test associations between MAO genes and a risk of PD. The data set includes 298 female discordant sibpairs and 348 male discordant sibpairs. For this study, all subjects analyzed were white and families with known parkin mutations were removed. We analyzed 15 single nucleotide polymorphisms (SNPs) and a dinucleotide repeat marker in the MAO genes. Association was found with the intron 13 SNP of MAOB in the female subset (P = 0.02). No significant association was found in the male subset. Our results add to the evidence of involvement of MAOB in PD and suggest that the effect may be stronger in women.

The lack of association between monoamine oxidase (MAO) intron 13 polymorphism and platelet MAO-B activity among men

Monoamine oxidase (MAO), a mitochondrial flavine containing enzyme, exists in two isoenzymes, MAO-A and MAO-B. Platelets contain MAO-B subtype, proposed to be a biomarker for different personality characteristics and vulnerability for substance abuse. The most common polymorphism of MAO-B gene, a single base change (A or G) occurs in intron 13. It has been proposed to be a functional polymorphism, controlling the activity of MAO-B in platelets. The aim of the study was to determine the association between platelet MAO-B activity and MAO-B intron 13 polymorphism in 225 racially and ethnically uniform healthy Caucasian men of the Croatian origin. Our results showed that platelet MAO-B activity did not differ between subjects subdivided into those with ≪A-allele≫ or ≪G-allele≫. This polymorphism of the MAO-B gene did not control the activity of the MAO-B in platelets. Platelet MAO-B activity was associated only with the smoking status, and it was significantly decreased in smokers when compared to nonsmokers. No significant association was found between MAO-B polymorphism and smoking status. In healthy individuals of the Croatian origin, the studied MAO-B polymorphism showed a lack of functional importance in regulating MAO-B activity in platelets. Since different populations may vary in the association between functional polymorphism and the MAO-B activity, and the genotype of transcription factor AP-2β was reported to be associated with altered platelet MAO-B activity, and with specific personality traits, further studies on different populations should be conducted to elucidate the molecular mechanism/s regulating platelet MAO-B activity.

Association analysis of the monoamine oxidase A and B genes with attention deficit hyperactivity disorder (ADHD) in an Irish sample: Preferential transmission of the MAO‐A 941G allele to affected children

Pharmacological and genetic studies suggest the importance of the dopaminergic, serotonergic, and noradrenergic systems in the pathogenesis of attention deficit hyperactivity disorder (ADHD). Monoamine oxidases A and B (MAO-A and MAO-B) degrade biogenic amines such as dopamine and serotonin and thereby control the levels of these neurotransmitters in the central nervous system. We examined four polymorphisms in the MAO-A gene (30 bp promoter VNTR, CA microsatellite in intron 2, 941G/T SNP in exon 8, and A/G SNP in intron 12) as well as two markers in the MAO-B gene (CA microsatellite in intron 2 and T/C SNP in intron 13) for association with ADHD in an Irish sample of 179 nuclear families. TDT analysis of the examined MAO-A markers revealed a significant association of the more active MAO-A 941G allele with the disorder (chi2 = 5.1, P = 0.03, OR = 1.7). In addition, haplotype analysis revealed a significantly increased transmission of a haplotype consisting of the shorter allele of the promoter VNTR (allele 1), the 6-repeat allele of the CA microsatellite and the G-allele of the 941G/T SNP (famhap global statistic 34.54, P = 0.01) to ADHD cases. No significant distortion in the number of transmitted alleles was observed between the two examined MAO-B polymorphisms and ADHD. These findings suggest the importance of the 941G/T MAO-A polymorphism in the development of ADHD at least in the Irish population.

Monoamine oxidases A and B gene polymorphisms in migraine patients

Abnormal cortical activity and brainstem functioning are considered the possible etiopathogenetic factors of migraine. Monoamine oxidase A and B (MAO-A and -B) regulate the levels of monoamine neurotransmitters, so changes in their activity could participate in migraine pathogenesis. We have investigated the possible association of MAO-A and -B alleles and haplotypes with two common types of migraine, i.e. migraine without aura (MO) and migraine with aura (MA), on the sample of 110 migraineours (80 MO and 30 MA) and 150 controls. MAO-A promoter and MAO-B intron 13 polymorphisms were genotyped by the PCR-based methods. In addition, we have reevaluated the reported association between MAO-B intron 13 polymorphism and platelet MAO-B activity. The platelet MAO-B activity was determined fluorimetrically using kynuramine as a substrate. We have found a tendency toward association of the shorter variant of MAO-A gene promoter with migraine without aura in male subjects. Regarding investigated MAO-B polymorphism, no association with migraine or with platelet MAO-B activity was found. The suggestive association of the variant in MAO-A gene with migraine is considered worthy of independent replication. On the other hand, further studies on MAO-B polymorphism in migraine do not seem promising.

Polymorphisms in the MAOA, MAOB, and COMT genes and aggressive behavior in schizophrenia.

Some studies have reported associations between COMT and MAO genotypes and aggression, though results have been inconsistent. We examined the relationship between Overt aggression scale (OAS) scores, and both MAOA and MAOB polymorphisms in a well-powered sample of 346 subjects with schizophrenia. We also examined COMT in a Stage II replication sample of 150 individuals, and combined these results with our previously reported (Stage I) findings for COMT. We found no evidence of any associations between OAS ratings and any of the polymorphisms investigated under different genetic models. There was no evidence of epistatic interaction between MAOA and COMT on OAS scores. These results fail to support the theory that functional polymorphisms within the MAOA, MAOB, or COMT genes, as determinants of catecholamine enzymatic activity, are risk factors for aggressive behavior.

Variations in the monoamine oxidase B (MAOB) gene are associated with Parkinson's disease.

The monoamine oxidase B gene (MAOB; Xp15.21-4) is a candidate gene for Parkinson's disease (PD) given its role in dopamine metabolism and its possible role in the activation of neurotoxins. The association of MAOB polymorphisms (a [GT] repeat allelic variation in intron 2 and an A-G transition in intron 13) with Parkinson's disease (PD) was studied in an Australian cohort of 204 (male:female ratio 1.60) people with PD and 285 (male:female ratio 1.64) age- and gender-matched control subjects. Genomic DNA was extracted from venous blood and polymerase chain reaction was used to amplify the appropriate regions of the MAOB gene. The length of each (GT) repeat sequence was determined by 5% polyacrylamide denaturing gel electrophoresis and a DNA fragment analyzer, while the G-A genotype was determined using 2% agarose gel electrophoresis. The G-A polymorphism showed no association with PD (odds ratio [OR] = 0.80; p = 0.51; 95% confidence interval [CI] = 0.42-1.53). There was a significant difference in allele frequencies of the (GT) repeat allelic variation between patients and control subjects (chi2 = 20.09; p<0.01). After statistical adjustment for potential confounders using a logistic regression analysis, the (GT) repeat alleles > or =188 base pairs in the intron 2 marker of the MAOB gene were significantly associated with PD (OR = 4.60; p<0.00005; 95% CI = 1.97-10.77). The 186 base pair allele was also significantly associated with PD (OR = 1.85; p = 0.048; 95% CI = 1.01-3.42). The GT repeat in intron 2 of the MAOB gene is a powerful marker for PD in this large Australian cohort.

Detection and Analysis of Four Polymorphic Markers at the Human Monoamine Oxidase (MAO) Gene in Japanese Controls and Patients with Parkinson's Disease

Monoamine oxidase (MAO), which exists in two forms (MAOA and MAOB), plays an important role in the oxidative metabolism of neurotransmitters such as dopamine, and has been implicated in the etiology of Parkinson's disease (PD). Individual variations in the activity of these enzymes appear to be genetically determined, and these genetic variations appear to be predominantly mediated by the MAO locus. Here, we detected and analyzed four polymorphic markers in the MAO gene using a polymerase chain reaction method in 228 Japanese controls (102 males and 126 females) and 68 patients with PD (30 males and 38 females). Although the analysis of the MAOA marker demonstrated no overall association between its alleles and PD, a significant difference in the frequency of one particular MAOA allele between controls and patients with PD was found. Moreover, in a comparison of the distribution of the full haplotypes at the MAOA locus, there was a significant difference in the frequency of one particular haplotype between male controls and patients with PD. In the MAOB polymorphism, there was no difference in the distribution of alleles between them. These findings support the hypothesis that the MAOA gene may affect the susceptibility of individuals to PD among MAOA polymorphic loci.