Low CD38 expression in lymphoblastoid cells and haplotypes are both associated with autism in a family-based study
Article first published online: 22 DEC 2010
Copyright © 2010, International Society for Autism Research, Wiley Periodicals, Inc.
Volume 3, Issue 6, pages 293–302, December 2010
How to Cite
Lerer, E., Levi, S., Israel, S., Yaari, M., Nemanov, L., Mankuta, D., Nurit, Y. and Ebstein, R. P. (2010), Low CD38 expression in lymphoblastoid cells and haplotypes are both associated with autism in a family-based study. Autism Res, 3: 293–302. doi: 10.1002/aur.156
- Issue published online: 22 DEC 2010
- Article first published online: 22 DEC 2010
- Manuscript Accepted: 19 JUL 2010
- Manuscript Received: 25 JAN 2010
- Autism Speaks and “Levi Eshkol” Scholarship
- autism spectrum disorder (ASD);
- gene expression;
- real time PCR;
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 (F = 17.2, P = 0.00024, df = 1). 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.