title: Monoamine oxidase B gene variants associated with attention deficit hyperactivity disorder in the Indo-Caucasoid population from West Bengal.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Manovikas Biomedical Research and Diagnostic Centre, 482, Madudah, Plot I-24, Sec.-J, E.M. Bypass, Kolkata, 700107, India.
authors.forename: Arijit
authors.initials: A
authors.lastname: Karmakar
authors.affiliation: Manovikas Biomedical Research and Diagnostic Centre, 482, Madudah, Plot I-24, Sec.-J, E.M. Bypass, Kolkata, 700107, India.
authors.forename: Subhamita
authors.initials: S
authors.lastname: Maitra
authors.affiliation: Manovikas Biomedical Research and Diagnostic Centre, 482, Madudah, Plot I-24, Sec.-J, E.M. Bypass, Kolkata, 700107, India.
authors.forename: Barnali
authors.initials: B
authors.lastname: Chakraborti
authors.affiliation: Manovikas Biomedical Research and Diagnostic Centre, 482, Madudah, Plot I-24, Sec.-J, E.M. Bypass, Kolkata, 700107, India.
authors.forename: Deepak
authors.initials: D
authors.lastname: Verma
authors.affiliation: Manovikas Biomedical Research and Diagnostic Centre, 482, Madudah, Plot I-24, Sec.-J, E.M. Bypass, Kolkata, 700107, India.
authors.forename: Swagata
authors.initials: S
authors.lastname: Sinha
authors.affiliation: Indian Institute of Chemical Biology-Council of Scientific & Industrial Research, Jadavpur, Kolkata, 700 032, India.
authors.forename: Kochupurackal P
authors.initials: KP
authors.lastname: Mohanakumar
authors.affiliation: Manovikas Biomedical Research and Diagnostic Centre, 482, Madudah, Plot I-24, Sec.-J, E.M. Bypass, Kolkata, 700107, India.
authors.forename: Usha
authors.initials: U
authors.lastname: Rajamma
authors.affiliation: Manovikas Biomedical Research and Diagnostic Centre, 482, Madudah, Plot I-24, Sec.-J, E.M. Bypass, Kolkata, 700107, India. kanchanmvk@yahoo.com.
authors.forename: Kanchan
authors.identifier: 0000-0002-4317-7522
authors.initials: K
authors.lastname: Mukhopadhyay
mesh_terms: D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000201:enzymology* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007194:India; D015810:Linkage Disequilibrium; D008297:Male; D008995:Monoamine Oxidase / Q000235:genetics*; D010641:Phenotype; D044465:White People / Q000235:genetics*
chemical_list: D008995:Monoamine Oxidase
keywords: ADHD; Conduct problems; Indo-Caucasoid population; Linkage disequilibrium; MAOB; Multifactor dimensionality reduction; rs56220155