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Prog Neuropsychopharmacol Biol Psychiatry. 2016 Nov 3;71:123-36. doi: 10.1016/j.pnpbp.2016.07.001. Epub 2016 Jul 2.

Genetic variants of MAOB affect serotonin level and specific behavioral attributes to increase autism spectrum disorder (ASD) susceptibility in males.

Author information

1
Manovikas Biomedical Research and Diagnostic Centre, Manovikas Kendra, 482 Madudah, Plot I-24, Sector J, EM Bypass, Kolkata, West Bengal 700107, India.
2
Out Patient Department, Manovikas Kendra, 482 Madudah, Plot I-24, Sector J, EM Bypass, Kolkata, West Bengal 700107, India.
3
Department of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, West Bengal, India.
4
Human Genetics Unit, Indian Statistical Institute, 203 B.T. Road, Kolkata, West Bengal, India.
5
Cell Biology and Physiology Division, Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Jadavpur, Kolkata, West Bengal, India.
6
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.

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.

KEYWORDS:

Autism spectrum disorder; Childhood autism rating scale; Hyperserotonemia; Male-bias; Monoamine oxidase B; Serotonin

PMID:
27381555
DOI:
10.1016/j.pnpbp.2016.07.001
[Indexed for MEDLINE]

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