Case-Control Haplotype Analysis Indicates Association of TPH1 Gene with Autism Spectrum Disorders (ASD) In the Indian Population

Thursday, May 17, 2012
Sheraton Hall (Sheraton Centre Toronto)
11:00 AM
A. S. Singh1, U. Rajamma1, S. Sinha2, A. Chatterjee2 and S. Ghosh3, (1)Manovikas Biomedical Research and Diagnostic Centre, Manovikas Kendra Rehabilitation and Research Institute for the Handicapped, Kolkata, India, (2)Out-Patient' Department, Manovikas Kendra Rehabilitation and Research Institute for the Handicapped, Kolkata, India, (3)Human Genetics Unit, Indian Statistical Institute, Kolkata, India
Background: ASD is a childhood complex neurodevelopmental disorder with high heritability in nature. Its prevalence rate is 1 in 91 individuals according to the latest report of 2009, which is much higher in comparison to 1 in 150 individuals as reported earlier in the same year. Platelet hyperserotonemia has been considered as an ASD endophenotype being one of the most consistent findings in ASD research indicating abnormalities in platelet serotonin system among individuals with ASD. Several candidate gene association studies had been carried out in wide number of different populations across the world to finding the genes involve in ASD; but the findings have not been conclusive due to bias results between different populations. Therefore, further investigation with more genetic markers is of absolute importance and TPH1 gene is one of the strong candidate genes for ASD hyperserotonemia, since its protein product tryptophan hydroxylase1 acts as rate limiting enzyme in the peripheral serotonin biosynthesis.

Objectives: Our present study is to investigate if there is any significant change in the TPH1 gene with individuals with ASD in the Indian population through genetic approach and also to compare our findings with the earlier reports. 

Methods: 486 subjects comprising 113 trios and 16 duo families with ASD along with 1 single, and 114 ethnically matched healthy controls (without any known neurological abnormalities) from West Bengal, India, were selected. Diagnosis was carried out using DSM-IV criteria while CARS was used for assessment.  Genotyping was performed with PCR-RFLP and PCR-DNA sequencing methods to examine four SNP markers rs211106, rs684302, rs623580 and rs10488682. Cocaphase and TDTphase of UNPHASED version 2.404 were used for polulation based case-control as well as family based association tests. 

Results: Population based case-control and family based TDT/HHRR analyses do not indicate any risk allele for the disorder. However, case-control haplotype analysis showed possible involvement of rs211106 and rs684302 (LRS = 14.6; DF = 3; p = 0.0022 and global p = 0.034) which suggest possible link of TPH1 with ASD.

Conclusions: Our data suggest that TPH1 is likely to involve in platelet hyperserotonemia of ASD in the Indian population and thereby pathophysiology of the disorder.

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