title: Macrophage migration inhibitory factor and autism spectrum disorders.
abstract: OBJECTIVE
  Autistic spectrum disorders are childhood neurodevelopmental disorders characterized by social and communicative impairment and repetitive and stereotypical behavior. Macrophage migration inhibitory factor (MIF) is an upstream regulator of innate immunity that promotes monocyte/macrophage-activation responses by increasing the expression of Toll-like receptors and inhibiting activation-induced apoptosis. On the basis of results of previous genetic linkage studies and reported altered innate immune response in autism spectrum disorder, we hypothesized that MIF could represent a candidate gene for autism spectrum disorder or its diagnostic components.
  
  
  METHODS
  Genetic association between autism spectrum disorder and MIF was investigated in 2 independent sets of families of probands with autism spectrum disorder, from the United States (527 participants from 152 families) and Holland (532 participants from 183 families). Probands and their siblings, when available, were evaluated with clinical instruments used for autism spectrum disorder diagnoses. Genotyping was performed for 2 polymorphisms in the promoter region of the MIF gene in both samples sequentially. In addition, MIF plasma analyses were conducted in a subset of Dutch patients from whom plasma was available.
  
  
  RESULTS
  There were genetic associations between known functional polymorphisms in the promoter for MIF and autism spectrum disorder-related behaviors. Also, probands with autism spectrum disorder exhibited higher circulating MIF levels than did their unaffected siblings, and plasma MIF concentrations correlated with the severity of multiple autism spectrum disorder symptoms.
  
  
  CONCLUSIONS
  These results identify MIF as a possible susceptibility gene for autism spectrum disorder. Additional research is warranted on the precise relationship between MIF and the behavioral components of autism spectrum disorder, the mechanism by which MIF contributes to autism spectrum disorder pathogenesis, and the clinical use of MIF genotyping.
authors.affiliation: Child Study Center, Department ofPsychology, Yale University, New Haven, Connecticut 06519, USA. elena.grigorenko@yale.edu
authors.forename: Elena L
authors.initials: EL
authors.lastname: Grigorenko
authors.forename: Summer S
authors.initials: SS
authors.lastname: Han
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Yrigollen
authors.forename: Lin
authors.initials: L
authors.lastname: Leng
authors.forename: Yuka
authors.initials: Y
authors.lastname: Mizue
authors.forename: George M
authors.initials: GM
authors.lastname: Anderson
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Mulder
authors.forename: Annelies
authors.initials: A
authors.lastname: de Bildt
authors.forename: Ruud B
authors.initials: RB
authors.lastname: Minderaa
authors.forename: Fred R
authors.initials: FR
authors.lastname: Volkmar
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Chang
authors.forename: Richard
authors.initials: R
authors.lastname: Bucala
mesh_terms: D000483:Alleles; D001321:Autistic Disorder / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics*; D008297:Male; D015999:Multivariate Analysis; D009426:Netherlands; D010375:Pedigree; D011110:Polymorphism, Genetic; D011379:Prognosis; D014481:United States
chemical_list: D008263:Macrophage Migration-Inhibitory Factors