title: Low CD38 expression in lymphoblastoid cells and haplotypes are both associated with autism in a family-based study.
abstract: 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.
authors.affiliation: Human Genetics, Hebrew University, Jerusalem, Israel.
authors.forename: Elad
authors.initials: E
authors.lastname: Lerer
authors.forename: Shlomit
authors.initials: S
authors.lastname: Levi
authors.forename: Salomon
authors.initials: S
authors.lastname: Israel
authors.forename: Maya
authors.initials: M
authors.lastname: Yaari
authors.forename: Lubov
authors.initials: L
authors.lastname: Nemanov
authors.forename: David
authors.initials: D
authors.lastname: Mankuta
authors.forename: Yirmiya
authors.initials: Y
authors.lastname: Nurit
authors.forename: Richard P
authors.initials: RP
authors.lastname: Ebstein
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000097:blood / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001321:Autistic Disorder / Q000097:blood / Q000235:genetics*; D018929:Cell Culture Techniques; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007557:Israel; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D055815:Young Adult
chemical_list: D051997:ADP-ribosyl Cyclase 1