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GABA A  receptor subunit genes  GABRB3, GABRA5 , and  GABRG3  located on chromosome 15q11-q13 have been implicated in the etiology of autistic spectrum disorders (ASD). This study intended to investigate the possible role of single-nucleotide polymorphisms (SNPs) present in  GABRB3  (rs2081648 and rs1426217),  GABRA5  (rs35586628), and  GABRG3  (rs208129) genes in ASD susceptibility and symptom-based and developmental phenotypes of ASD in Chinese Han children and adolescents. 99 ASD patients and 231 age- and gender- frequency-matched typical developing (TD) controls were tested by TaqMan® genotyping assay. Symptom-based phenotypes were evaluated by Childhood Autism Rating Scale (CARS) and Autism Behavior Checklist (ABC), and developmental phenotypes were assessed by Early Childhood Development Questionnaire (ECDQ) in ASD patients. Three haplotypes and global  χ    2   test of all SNPs demonstrated significant associations between ASD and TD groups. Besides,  GABRB3  rs2081648,  GABRA5  rs35586628, and  GABRG3  rs208129 polymorphisms were associated with symptom-based deficits in social interaction, sensorimotor and somatosensory coordination, visual response, imitation, activity level, language expression and adaptability. Developmental abnormalities in late emergences of social interaction and fine motor were detected in  GABRB3  rs2081648 polymorphism. Overall results indicated that gene synergy may participate in ASD pathogenesis, and GABA A  receptor gene polymorphisms can predict symptom-based and developmental deficits in ASD individuals.

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GABAA receptor subunit gene polymorphisms predict symptom-based and developmental deficits in Chinese Han children and adolescents with autistic spectrum disorders