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

• Published in: BMC medical genetics Vol. 18; no. 1; p. 109
• Main Authors: Karmakar, Arijit, Goswami, Rishov, Saha, Tanusree, Maitra, Subhamita, Roychowdhury, Anirban, Panda, Chinmay Kumar, Sinha, Swagata, Ray, Anirban, Mohanakumar, Kochupurackal P, Rajamma, Usha, Mukhopadhyay, Kanchan
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 05.10.2017; BioMed Central; BMC
• Subjects: ADHD; Age; Alleles; Amine oxidase (flavin-containing); Analysis; Attention Deficit Disorder with Hyperactivity - diagnosis; Attention Deficit Disorder with Hyperactivity - genetics; Attention deficit hyperactivity disorder; Behavior; Behavioral trait; Children; Data processing; Development and progression; Diagnostic and Statistical Manual of Mental Disorders; DNA sequencing; Dopamine; Etiology; European Continental Ancestry Group - genetics; Families & family life; Female; Females; Genes; Genetic aspects; Genetic Predisposition to Disease; Genetic variation; Genotyping; Genotyping Techniques; Haplotypes; Heritability; Humans; Hyperactivity; Impulsive behavior; Impulsivity; Isoenzymes; Male; MAOA; MAOB; Maternal transmission; Mental disorders; Metabolism; Minority & ethnic groups; Mitochondria; Monoamine oxidase; Monoamine Oxidase - genetics; Neurosciences; Neurotransmitters; Norepinephrine; Physiological aspects; Pilot Projects; Pregnancy; Problem Behavior - psychology; Serotonin; Statistical analysis; Statistics; India; ADHD; Maternal age; Genotyping; MAOB; MAOA; Linkage disequilibrium; Behavioral trait; Indo-Caucasoid population; Maternal transmission
• ISSN: 1471-2350; 1471-2350
• DOI: 10.1186/s12881-017-0469-5

Attention 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. Subjects 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. Out 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. It 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.