Title

Genetic Association And Gene-Gene Interaction Analyses Suggest Likely Involvement Of Itgb3 And Tph2 With Autism Spectrum Disorder (Asd) In The Indian Population

Keywords

Autism; Autism spectrum disorder; Gene-gene interaction; Genetic association; Haplotype; TDT

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. Conclusion: Overall results of the present study indicate likely involvement of ITGB3 and TPH2 in the pathophysiology of ASD in the Indian population. © 2013 Elsevier Inc..

Publication Date

8-1-2013

Publication Title

Progress in Neuro-Psychopharmacology and Biological Psychiatry

Volume

45

Number of Pages

131-143

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1016/j.pnpbp.2013.04.015

Socpus ID

84878853454 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/84878853454

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