title: Genetic variants of MAOB affect serotonin level and specific behavioral attributes to increase autism spectrum disorder (ASD) susceptibility in males.
abstract: Serotonergic system participates in various developmental processes and modulation of behaviour. Autism Spectrum Disorder (ASD) is characterized by a range of behavioral symptoms scaling from mild to severe. Abnormal 5-HT synthesis and signalling, platelet hyperserotonemia and amelioration of repetitive behaviours by SSRI are some of the key findings, which reinforced the hypothesis that serotonergic genes might act as ASD susceptible genes. Therefore, genes encoding monoamine oxidases A/B (MAOA/MAOB) received special attention as these genes are located on the X-chromosome and the gene products are responsible for 5-HT degradation. In the present study, we conducted population-based association analysis of eight markers of MAOB with ASD in a study cohort of 203 cases and 236 controls form India and examined its effect on platelet 5-HT content and behaviour. Gender-specific changes were observed for the contrasting LD between pair of markers among cases and controls. Case-control analysis demonstrated over-distribution of major C allele of rs2283728 and rs2283727 in male and female ASD cases respectively. Haplotypic distribution and interaction among markers showed more robust effect in male cases. Interestingly, male ASD cases displayed higher platelet 5-HT content in comparison to the respective controls. Quantitative trait analysis revealed significant correlation of genetic variants and haplotypes of MAOB markers, rs1799836 and rs6324 with increased platelet 5-HT level and CARS scores for specific behavioral symptoms respectively in males. This study suggests that MAOB increases ASD risk in males, possibly through its sex-specific regulatory effect on 5-HT metabolism and behavior.
authors.affiliation: Manovikas Biomedical Research and Diagnostic Centre, Manovikas Kendra, 482 Madudah, Plot I-24, Sector J, EM Bypass, Kolkata, West Bengal 700107, India.
authors.forename: Barnali
authors.initials: B
authors.lastname: Chakraborti
authors.affiliation: Manovikas Biomedical Research and Diagnostic Centre, Manovikas Kendra, 482 Madudah, Plot I-24, Sector J, EM Bypass, Kolkata, West Bengal 700107, India.
authors.forename: Deepak
authors.initials: D
authors.lastname: Verma
authors.affiliation: Manovikas Biomedical Research and Diagnostic Centre, Manovikas Kendra, 482 Madudah, Plot I-24, Sector J, EM Bypass, Kolkata, West Bengal 700107, India.
authors.forename: Arijit
authors.initials: A
authors.lastname: Karmakar
authors.affiliation: Manovikas Biomedical Research and Diagnostic Centre, Manovikas Kendra, 482 Madudah, Plot I-24, Sector J, EM Bypass, Kolkata, West Bengal 700107, India.
authors.forename: Preeti
authors.initials: P
authors.lastname: Jaiswal
authors.affiliation: Manovikas Biomedical Research and Diagnostic Centre, Manovikas Kendra, 482 Madudah, Plot I-24, Sector J, EM Bypass, Kolkata, West Bengal 700107, India.
authors.forename: Aritrika
authors.initials: A
authors.lastname: Sanyal
authors.affiliation: Manovikas Biomedical Research and Diagnostic Centre, Manovikas Kendra, 482 Madudah, Plot I-24, Sector J, EM Bypass, Kolkata, West Bengal 700107, India.
authors.forename: Debarshi
authors.initials: D
authors.lastname: Paul
authors.affiliation: Out Patient Department, Manovikas Kendra, 482 Madudah, Plot I-24, Sector J, EM Bypass, Kolkata, West Bengal 700107, India.
authors.forename: Swagata
authors.initials: S
authors.lastname: Sinha
authors.affiliation: Manovikas Biomedical Research and Diagnostic Centre, Manovikas Kendra, 482 Madudah, Plot I-24, Sector J, EM Bypass, Kolkata, West Bengal 700107, India.
authors.forename: Asem Surindro
authors.initials: AS
authors.lastname: Singh
authors.affiliation: Manovikas Biomedical Research and Diagnostic Centre, Manovikas Kendra, 482 Madudah, Plot I-24, Sector J, EM Bypass, Kolkata, West Bengal 700107, India.
authors.forename: Subhrangshu
authors.initials: S
authors.lastname: Guhathakurta
authors.affiliation: Department of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, West Bengal, India.
authors.forename: Anirban
authors.initials: A
authors.lastname: Roychowdhury
authors.affiliation: Department of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, West Bengal, India.
authors.forename: Chinmoy Kumar
authors.initials: CK
authors.lastname: Panda
authors.affiliation: Human Genetics Unit, Indian Statistical Institute, 203 B.T. Road, Kolkata, West Bengal, India.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Cell Biology and Physiology Division, Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Jadavpur, Kolkata, West Bengal, India.
authors.forename: Kochupurackal P
authors.initials: KP
authors.lastname: Mohanakumar
authors.affiliation: Manovikas Biomedical Research and Diagnostic Centre, Manovikas Kendra, 482 Madudah, Plot I-24, Sector J, EM Bypass, Kolkata, West Bengal 700107, India.
authors.forename: Kanchan
authors.initials: K
authors.lastname: Mukhophadhyay
authors.affiliation: Manovikas Biomedical Research and Diagnostic Centre, Manovikas Kendra, 482 Madudah, Plot I-24, Sector J, EM Bypass, Kolkata, West Bengal 700107, India. Electronic address: ushamvk@yahoo.co.in.
authors.forename: Usha
authors.initials: U
authors.lastname: Rajamma
mesh_terms: D000293:Adolescent; D000328:Adult; D000067877:Autism Spectrum Disorder / Q000097:blood / Q000150:complications / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007194:India; D008297:Male; D001523:Mental Disorders / Q000209:etiology*; D008995:Monoamine Oxidase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D012701:Serotonin / Q000097:blood*; D012737:Sex Factors; D055815:Young Adult
chemical_list: D012701:Serotonin; D008995:Monoamine Oxidase
keywords: Autism spectrum disorder; Childhood autism rating scale; Hyperserotonemia; Male-bias; Monoamine oxidase B; Serotonin