摘要Background The reasons behind the cardinal symptoms of communication deficits and repetitive,stereotyped behaviors that characterize autism spectrum disorder(ASD)remain unknown.The dopamine(DA)system,which regulates motor activity,goal-directed behaviors,and reward function,is believed to play a crucial role in ASD,although the exact mechanism is still unclear.Investigations have shown an association of the dopamine receptor D4(DRD4)with various neurobehavioral disorders.Methods We analyzed the association between ASD and four DRD4 genetic polymorphisms,5'flanking 120-bp duplication(rs4646984),rs1800955 in the promoter,exon 1 12 bp duplication(rs4646983),and exon 3 48 bp repeats.We also examined plasma DA and its metabolite levels,DRD4 mRNA expression,and correlations of the studied polymorphisms with these parameters by case-control comparative analyses.The expression of DA transporter(DAT),which is important in regulating the circulating DA level,was also evaluated.Results A significantly higher occurrence of rs1800955"T/TT"was observed in the probands.ASD traits were affected by rs1800955"T"and the higher repeat alleles of the exon 3 48 bp repeats,rs4646983 and rs4646984.ASD probands exhibited lower DA and norepinephrine levels together with higher homovanillic acid levels than the control subjects.DAT and DRD4 mRNA expression were down-regulated in the probands,especially in the presence of DAT rs3836790"6R"and rs27072"CC"and DRD4 rs4646984 higher repeat allele and rs1800955"T".Conclusion This pioneering investigation revealed a positive correlation between genetic variants,hypodopaminergic state,and impairment in socio-emotional and communication reciprocity in Indian subjects with ASD,warranting further in-depth analysis.