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

Abstract

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.

Case-Control Study of the Effects of Gut Microbiota Composition on Neurotransmitter Metabolic Pathways in Children With Attention Deficit Hyperactivity Disorder

“…Previous studies have reported that ADHD pathogenesis may be associated with dysregulation of neurotransmitters such as dopamine, serotonin (5-hydroxytryptamine, 5-HT), and norepinephrine (Magula et al, 2019;Stewart et al, 2019;Suzuki et al, 2019). Others have shown that the incidence of ADHD may have a certain degree of heritability, and genes related to dopamine, norepinephrine, and 5-HT transmission have been found to be abnormally expressed in children with ADHD (Banerjee and Nandagopal, 2015;Karmakar et al, 2017;Kim et al, 2018). Although various theories have been proposed, the pathogenetic mechanisms underlying ADHD have not been fully clarified, which limits the development of new treatments.…”

miR‐522 facilitates the prosperities of endometrial carcinoma cells by directly binding to monoamine oxidase B

“…26,27 Growing reports disclosed that miR-522 is nor- MAOB and MAOA have dramatic influence in the etiology of many neurological diseases. 18,19 Moreover, Liao et al 30 have proved that MAOA was involved in the development of adenocarcinoma.…”

“…Monoamine oxidase B (MAOB) is well known as a member of monoamine oxidase family that affects the etiology of many neurological diseases . The MAOB enzyme is located in the outer of mitochondrial membrane.…”

“…Monoamine oxidase B (MAOB) is well known as a member of monoamine oxidase family that affects the etiology of many neurological diseases. 18,19 The MAOB enzyme is located in the outer of mitochondrial membrane. It has been previously reported that the activity of mitochondria is related with the G/A polymorphism in intron 13 of the MAOB gene.…”

Association of Monoamine Oxidase A (MAOA) Gene uVNTR and rs6323 Polymorphisms with Attention Deficit and Hyperactivity Disorder in Korean Children

“…Recently, Karmakar et al (2017) found that the MAOA gene rs6323 polymorphism was associated with behavioral problems in ADHD males in the Indian population [25]. These polymorphisms (uVNTR and rs6323) are known to be functional and affect the activities of MAOA enzymes [26,27].…”