Functional SLC6A3 polymorphisms differentially affect autism spectrum disorder severity: a study on Indian subjects.

Imbalance in dopamine (DA) signaling is proposed to play a potential role in the etiology of Autism spectrum disorder (ASD) since, as a neuromodulator, DA regulates executive function, motor activity, social peering, attention as well as perception and subjects with ASD often exhibit deficit in these traits. Level of DA in the synaptic cleft is maintained by dopamine transporter (DAT) and hence, to identify the role of DAT in ASD, we have analyzed four functional genetic variants, rs28363170, rs3836790, rs2652511, rs27072, in nuclear families with ASD probands. Subjects were diagnosed based on Diagnostic and Statistical Manual for Mental Disorders and trait severity was assessed by Childhood Autism Rating Scale 2-Standard test. Informed written consent was obtained from the parents/care givers before recruitment followed by collection of peripheral blood for genomic DNA isolation. Target sites were investigated by PCR-based methods and data obtained was analyzed by population- as well as family-based statistical methods. Case-control analysis revealed significant higher frequencies of 9 repeat (9R) and 5 repeat (5R) alleles of rs28363170 and rs3836790 respectively in the ASD probands. Family-based analysis showed statistically significant higher paternal transmission of rs28363170 9R and rs2652511 T alleles. In the presence of rs28363170 9R, rs27072 C, rs3836790 6R6R, and rs2652511 CC variants, trait scores were higher. Studied variants showed independent as well as interactive effects, which varied based on gender of the probands. We infer that altered DA availability mediated through DAT may affect autistic traits warranting further in depth investigation in the field.