BACKGROUND: Impairments in social processes characterize one of the core 
deficits in autism spectrum disorders (ASD) and accumulating evidence suggests 
that oxytocin neurotransmission is implicated in mediating social adaptation in 
ASD. Using a mouse model, CD38, a transmembrane protein expressed in immune 
cells but also in brain, was found to be critical for social behavior via 
regulation of oxytocin secretion. This prompted us to both examine CD38 
expression in human lymphoblastoid cell lines (LBC) as well as to test 
association between SNPs across the CD38 gene and ASD.
METHODS: LBC’s were derived from 44 ASD lines and 40 "unaffected" parents. 
Family-based association (UNPHASED) was examined by genotyping 11 tagging SNPs 
spanning the CD38 gene identified using HapMap data in 170 trios. An additional 
SNP (rs3796863) associated in a study by Munesue et al. with ASD was also 
genotyped.
RESULTS: A highly significant reduction in CD38 expression was observed in 
immortalized lymphocytes derived from ASD subjects compared to their 
"unaffected" parents (F517.2, P50.00024, df51). Haplotype analysis showed 
significant association (permutation corrected) between three and seven locus 
haplotypes and DSM IV ASD in low functioning (IQ < 70) subjects.
CONCLUSIONS: The current report supports a role for CD38 in conferring risk for 
ASD. Notably, our study shows that this gene is not only associated with low 
functioning ASD but that CD38 expression is markedly reduced in LBC derived from 
ASD subjects compared to "unaffected" parents, strengthening the connection 
between oxytocin and ASD.