title: Genetic association and gene-gene interaction analyses suggest likely involvement of ITGB3 and TPH2 with autism spectrum disorder (ASD) in the Indian population.
abstract: BACKGROUND
  Serotoninergic dysfunction leads to neurodevelopmental abnormalities and behavioral impairments. Platelet hyperserotoninemia is reported as the best identified endophenotype for autism spectrum disorders. Therefore, in the present study we investigate the association of TPH2, the rate limiting enzyme in 5-HT biosynthesis and ITGB3, a serotonin quantitative trait locus with ASD in the Indian population.
  
  
  METHODS
  Population and family-based genetic association and gene-gene interaction analyses were performed to evaluate the role of ITGB3 and TPH2 markers in ASD etiology.
  
  
  RESULTS
  Association tests using ITGB3 markers revealed significant paternal overtransmission of T allele of rs5918 to male probands. Interestingly for TPH2, we observed significant overrepresentation of A-A (rs11179000-rs4290270), G-A (rs4570625-rs4290270), G-G-A (rs4570625-rs11179001-rs4290270) and A-G-A (rs11179000-rs11179001-rs4290270) haplotypes in the controls and maternal preferential transmission of A-A (rs11179001-rs7305115), T-A-A (rs4570625-rs11179001-rs7305115) and T-A-A (rs11179000-rs11179001-rs7305115) and nontransmission of G-G-A (rs4570625-rs11179001-rs7305115) haplotypes to the affected offspring. Moreover, interaction of ITGB3 marker, rs15908 with TPH2 markers was found to be significant and influenced by the sex of the probands. Predicted individual risk, which varied from very mild to moderate, supports combined effect of these markers in ASD.
  
  
  CONCLUSIONS
  Overall results of the present study indicate likely involvement of ITGB3 and TPH2 in the pathophysiology of ASD in the Indian population.
authors.affiliation: Manovikas Biomedical Research & Diagnostic Centre, Manovikas Kendra, 482 Madudah, Plot I-24, Sector J, EM bypass, Kolkata, West Bengal, India. asemsuren@gmail.com
authors.forename: Asem Surindro
authors.initials: AS
authors.lastname: Singh
authors.forename: Rashmi
authors.initials: R
authors.lastname: Chandra
authors.forename: Subhrangshu
authors.initials: S
authors.lastname: Guhathakurta
authors.forename: Swagata
authors.initials: S
authors.lastname: Sinha
authors.forename: Anindita
authors.initials: A
authors.lastname: Chatterjee
authors.forename: Shabina
authors.initials: S
authors.lastname: Ahmed
authors.forename: Saurabh
authors.initials: S
authors.lastname: Ghosh
authors.forename: Usha
authors.initials: U
authors.lastname: Rajamma
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics*; D004843:Epistasis, Genetic / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007194:India; D039661:Integrin beta3 / Q000235:genetics*; D008297:Male; D010290:Parents; D014365:Tryptophan Hydroxylase / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: C061248:ITGB3 protein, human; D039661:Integrin beta3; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase
keywords: ASD; Autism; Autism spectrum disorder; FASTSNP; Genetic association; Gene–gene interaction; Haplotype; ITGB3; LD; MDR; STRING; Search Tool for the Retrieval of Interacting Genes; TDT; TPH2; autism spectrum disorder; function analysis and selection tool for single nucleotide; integrin beta chain 3; linkage disequilibrium; multifactor dimensionality reduction; transmission disequilibrium test; tryptophan hydroxylase 2