P01-190 - Molecular Genetic Study on MAOA and SLC6A4 in Association with Intellectual Disability Associated Behavioral Problems

Abstract

Objective

Intellectual disability (ID) is defined as significantly subaverage intellectual functioning with deficits in adaptive behavior. For ∼40% of individuals, cause for disability remains unknown and these are categorized as idiopathic ID (IID). Various behavioral problems co-occur with ID and thus serotonergic neurotransmission, known to control emotion, mood and drive, has received immense attention. Synaptic serotonin (5-HT) level is primarily maintained by metabolizing enzyme MAOA and serotonin transporter (SLC6A4) which helps in reuptake of the neurotransmitter. Since functional genetic polymorphisms have a potency to affect activities of these proteins, in the present investigation polymorphisms in these genes (MAOA-u VNTR, rs6323, 5-HTTLPR and STIN2) have been analyzed in IID individuals associated with various behavioral problems.

Methods

Families (N=189) with IID probands were recruited following DSM-IV. After obtaining informed written consent for participation, peripheral blood was collected for isolation of genomic DNA used for PCR-based genotyping of target sites followed by family-based statistical analyses of data.

Results

Significant association of MAOA rs6323 “T” allele with female IID (P=0.016) and a trend towards association with female IID patients exhibiting behavioral problems (P=0.046) was noticed. Non significant over transmission of the 5-HTTLPR “L” allele was also observed in female IID probands with behavioral problems (P=0.076). Synergistic epistatic interaction, with a sex-bias, was noticed between MAOA and 5-HTT (P< 0.05).

Conclusions

From the data obtained it could be summarized that serotonergic system may have some role in the etiology of behavioral problems of female IID individuals.