Research output: Contribution to journal › Article › peer-review
Macrophage migration inhibitory factor and autism spectrum disorders. / Grigorenko, Elena L.; Han, Summer S.; Yrigollen, Carolyn M.; Leng, Lin; Mizue, Yuka; Anderson, George M.; Mulder, Erik J.; De Bildt, Annelies; Minderaa, Ruud B.; Volkmar, Fred R.; Chang, Joseph T.; Bucala, Richard.
In: Pediatrics, Vol. 122, No. 2, 08.2008, p. e438-e445.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Macrophage migration inhibitory factor and autism spectrum disorders
AU - Grigorenko, Elena L.
AU - Han, Summer S.
AU - Yrigollen, Carolyn M.
AU - Leng, Lin
AU - Mizue, Yuka
AU - Anderson, George M.
AU - Mulder, Erik J.
AU - De Bildt, Annelies
AU - Minderaa, Ruud B.
AU - Volkmar, Fred R.
AU - Chang, Joseph T.
AU - Bucala, Richard
PY - 2008/8
Y1 - 2008/8
N2 - 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.
AB - 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.
KW - ASD
KW - Autism spectrum disorder
KW - Genetic association
KW - Genetic polymorphisms
KW - Immunologic insult
KW - MIF
KW - Neurodevelopmental disorders
UR - http://www.scopus.com/inward/record.url?scp=49849104918&partnerID=8YFLogxK
U2 - 10.1542/peds.2007-3604
DO - 10.1542/peds.2007-3604
M3 - Article
C2 - 18676531
AN - SCOPUS:49849104918
VL - 122
SP - e438-e445
JO - Pediatrics
JF - Pediatrics
SN - 0031-4005
IS - 2
ER -
ID: 87393213