Potential Contribution of Monoamine Oxidase A Gene Variants in ADHD and Behavioral Co-Morbidities: Scenario in Eastern Indian Probands

Karmakar, Arijit; Maitra, Subhamita; Verma, Deepak; Chakraborti, Barnali; Goswami, Rishov; Ghosh, Paramita M.; Sinha, Swagata; Mohanakumar, Kochupurackal P.; Rajamma, Usha; Mukhopadhyay, Kanchan

doi:10.1007/s11064-014-1276-4

Cited by 11 publications

(12 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Keck Foundation Biotechnology Resource Laboratory at Yale University; http://ycga.yale.edu/). This MAOA SNP, located at the position 43294463 MFA 0.338, has previously been linked to antisocial personality disorder in adult females (Ducci et al, 2008), inattention-hyporeactivity levels among children (Karmakar et al, 2014), autism spectrum disorder (Verma et al, 2014), and the efficacy of antidepressants (Peters, Slager, McGrath, Knowles, & Hamilton, 2004). This SNP has yet to be linked to aggression, though its inclusion in the MAOA gene suggests it may exhibit just such an association.…”

Section: Methodsmentioning

confidence: 99%

Monoamine oxidase A (MAOA) genotype predicts greater aggression through impulsive reactivity to negative affect

Chester

DeWall

Derefinko

et al. 2015

Behavioural Brain Research

View full text Add to dashboard Cite

Low functioning MAOA genotypes have been reliably linked to increased reactive aggression, yet the psychological mechanisms of this effect remain largely unknown. The low functioning MAOA genotype’s established link to diminished inhibition and greater reactivity to conditions of negative affect suggest that negative urgency, the tendency to act impulsively in the context of negative affect, may fill this mediating role. Such MAOA carriers may have higher negative urgency, which may in turn predict greater aggressive responses to provocation. To test these hypotheses, 277 female and male participants were genotyped for an MAOA SNP yet to be linked to aggression (rs1465108), and then reported their negative urgency and past aggressive behavior. We replicated the effect of the low functioning MAOA genotype on heightened aggression, which was mediated by greater negative urgency. These results suggest that disrupted serotonergic systems predispose individuals towards aggressive behavior by increasing impulsive reactivity to negative affect.

show abstract

Section: Methodsmentioning

confidence: 99%

Monoamine oxidase A (MAOA) genotype predicts greater aggression through impulsive reactivity to negative affect

Chester

DeWall

Derefinko

et al. 2015

Behavioural Brain Research

View full text Add to dashboard Cite

show abstract

“…Several MAOA variants have showed association with ADHD in various populations, including the Indo-Caucasoid population [ 30 , 31 ]. MAOB gene variants have also been studied, though the numbers of variants investigated were few and the data obtained were inconsistent [ 24 , 28 , 32 – 37 ].…”

Section: Introductionmentioning

confidence: 99%

Monoamine oxidase B gene variants associated with attention deficit hyperactivity disorder in the Indo-Caucasoid population from West Bengal

et al. 2016

View full text Add to dashboard Cite

Background: Attention deficit hyperactivity disorder (ADHD) is characterized by symptoms of inattention, excessive motor activity and impulsivity detected mostly during childhood. These traits are known to be controlled by monoamine neurotransmitters, chiefly dopamine, serotonin and norepinephrine. Monoamine oxidase A (MAOA) and B (MAOB), two isoenzymes bound to the outer membrane of mitochondria, are involved in the degradation of monoamines and were explored for association with ADHD in different ethnic groups. In the present study, few exonic as well as intronic MAOB variants were analyzed in ADHD probands (N = 150) and ethnically matched controls (N = 150) recruited following the Diagnostic and Statistical Manual for Mental Disorders-4 th edition (DSM-IV). Appropriate scales were used for measuring the behavioural attributes. Gene variants were analyzed by amplification of target sites followed by DNA sequencing and data obtained were analyzed by population based statistical methods. Results: Out of 34 variants present in the analyzed sites, only seven functional variants, rs4824562, rs56220155, rs2283728, rs2283727, rs3027441, rs6324 and rs3027440, were found to be polymorphic. rs2283728 'C' (P = 3.45e-006) and rs3027440 'T' (P = 0.02) alleles showed higher frequencies in ADHD probands as compared to controls. rs56220155 ' A' (P = 0.04) allele and 'GA' (P = 0.04) genotype showed higher frequencies in the male and female ADHD probands respectively as compared to sex-matched controls. Analysis of pairwise linkage disequilibrium revealed striking differences between probands and controls. Haplotype analysis revealed significantly higher occurrence of different haplotypes in the ADHD probands while some haplotypes were detected in the controls only. Higher scores for conduct problems were found to be associated with rs56220155 ' A' (P = 0.05) allele in the male ADHD probands. Multifactor dimensionality reduction analysis showed independent as well as interactive effects of polymorphic variants which were more robust in the male probands. Conclusions: Since all the polymorphic variants analyzed were functional, it may be inferred that MAOB gene variants are contributing to the etiology of ADHD in the Indo-Caucasoid population from eastern India which merits further in depth analysis.

show abstract

“…The target regions were amplified via polymerase chain reaction (PCR) using oligonucleotides designed in the lab using the Primer3 software [ 55 ] and the amplicons were utilized for genotyping the samples either through gel electrophoresis or using Sanger sequencing by capillary electrophoresis method [ 56 ]. For sequence analysis of the amplicons, Applied Biosystems 3130 Genetic Analyzer was used [ 48 , 49 ]. Chromatograms were also analyzed manually and for the identification of heterozygous SNPs, >25% base calling was accepted.…”

Section: Methodsmentioning

confidence: 99%

“…Chromatograms were also analyzed manually and for the identification of heterozygous SNPs, >25% base calling was accepted. Detailed analytic protocols for PCR amplification and genotyping were published earlier [ 48 , 49 ].…”

Section: Methodsmentioning

confidence: 99%

“…However, worldwide only a few MAOA and MAOB gene variants were studied and the data obtained were neither consistent nor conclusive [ 31 , 35 , 37 , 44 – 47 ]. Our population-based analysis on 58 MAO gene variants revealed association of a number of variants with ADHD [ 48 , 49 ]. Due to high heritability of ADHD traits, in the present study all these variants were explored to identify familial transmission pattern.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pilot study indicate role of preferentially transmitted monoamine oxidase gene variants in behavioral problems of male ADHD probands

et al. 2017

View full text Add to dashboard Cite

BackgroundAttention deficit hyperactivity disorder (ADHD) is an etiologically complex childhood onset neurobehavioral disorder characterized by age-inappropriate inattention, hyperactivity, and impulsivity. Symptom severity varies widely and boys are diagnosed more frequently than girls. ADHD probands were reported to have abnormal transmissions of dopamine, serotonin, and/or noradrenaline. Monoamine oxidase A (MAOA) and B (MAOB), mitochondrial outer membrane bound two isoenzymes, mediate degradation of these neurotransmitters and thus regulating their circulating levels. Case-control analyses in different populations, including Indians, suggested involvement of MAOA and MAOB genes in the etiology of ADHD. Due to high heritability rate of ADHD, we tested familial transmission of MAOA and MAOB variants to ADHD probands in 190 nuclear families having ADHD probands from Indo-Caucasoid ethnicity.MethodsSubjects were recruited following the Diagnostic and Statistical Manual of Mental Disorders-4th edition (DSM-IV). Appropriate scales were used for measuring the behavioral traits in probands. Genotyping was performed through PCR-based amplification of target sites followed by DNA-sequencing and/or gel-electrophoresis. Data obtained were analyzed by family based statistical methods.ResultsOut of 58 variants present in the analyzed sites only 15 were found to be polymorphic (30 bp-uVNTR, rs5906883, rs1465107, rs1465108, rs5905809, rs5906957, rs6323, rs1137070 from MAOA and rs4824562, rs56220155, rs2283728, rs2283727, rs3027441, rs6324, rs3027440 from MAOB). Statistically significant maternal transmission of alleles to male probands was observed for MAOA rs5905809 ‘G’ (p = 0.04), rs5906957 ‘A’ (p = 0.04), rs6323 ‘G’ (p = 0.0001) and MAOB rs56220155 ‘A’ (p = 0.002), rs2283728 ‘C’ (p = 0.0008), rs2283727 ‘C’ (p = 0.0008), rs3027441 ‘T’ (p = 0.003), rs6324 ‘C’ (p = 0.003), rs3027440 ‘T’ (p = 0.0002). Significantly preferential maternal transmissions of different haplotype combinations to male probands were also noticed (p < 0.05), while female probands did not reveal such transmission bias. Behavioral traits of male probands exhibited significant association with gene variants. Age of the mother at pregnancy also revealed association with risk variants of male probands.ConclusionsIt may be inferred that the MAOA and MAOB variants may contribute to the etiology of ADHD in the Indo-Caucasoid population and could be responsible for higher occurrence of ADHD in the boys.Electronic supplementary materialThe online version of this article (10.1186/s12881-017-0469-5) contains supplementary material, which is available to authorized users.

show abstract

Potential Contribution of Monoamine Oxidase A Gene Variants in ADHD and Behavioral Co-Morbidities: Scenario in Eastern Indian Probands

Cited by 11 publications

References 72 publications

Monoamine oxidase A (MAOA) genotype predicts greater aggression through impulsive reactivity to negative affect

Monoamine oxidase A (MAOA) genotype predicts greater aggression through impulsive reactivity to negative affect

Monoamine oxidase B gene variants associated with attention deficit hyperactivity disorder in the Indo-Caucasoid population from West Bengal

Pilot study indicate role of preferentially transmitted monoamine oxidase gene variants in behavioral problems of male ADHD probands

Contact Info

Product

Resources

About