Correlations Between Gene Expression and Mercury Levels in Blood of Boys With and Without Autism

• Published in: Neurotoxicity research 2011-01, Vol.19 (1), p.31-48
• Main Authors: Stamova, Boryana, Green, Peter G., Tian, Yingfang, Hertz-Picciotto, Irva, Pessah, Isaac N., Hansen, Robin, Yang, Xiaowei, Teng, Jennifer, Gregg, Jeffrey P., Ashwood, Paul, Van de Water, Judy, Sharp, Frank R.
• Format: Article
• Language: English
• Subjects: Amino acids; Antigen presentation; Autism; Autistic Disorder - blood; Autistic Disorder - diagnosis; Autistic Disorder - genetics; Biomedical and Life Sciences; Biomedicine; Blood; Cell Biology; Cell death; Child Development; Child, Preschool; Children; Cytology; Data processing; DNA microarrays; Gene expression; Gene Expression Regulation, Developmental; Gene Regulatory Networks - physiology; Genomes; Humans; Lead; Male; Mercury; Mercury - blood; Metabolism; Neurobiology; Neurochemistry; Neurology; Neurosciences; Neurotoxicity; Pharmacology/Toxicology; RNA; Toxicants; Transcription
• ISSN: 1029-8428; 1476-3524
• DOI: 10.1007/s12640-009-9137-7

Gene expression in blood was correlated with mercury levels in blood of 2- to 5-year-old boys with autism (AU) compared to age-matched typically developing (TD) control boys. This was done to address the possibility that the two groups might metabolize toxicants, such as mercury, differently. RNA was isolated from blood and gene expression assessed on whole genome Affymetrix Human U133 expression microarrays. Mercury levels were measured using an inductively coupled plasma mass spectrometer. Analysis of covariance (ANCOVA) was performed and partial correlations between gene expression and mercury levels were calculated, after correcting for age and batch effects. To reduce false positives, only genes shared by the ANCOVA models were analyzed. Of the 26 genes that correlated with mercury levels in both AU and TD boys, 11 were significantly different between the groups ( P (Diagnosis*Mercury) ≤ 0.05). The expression of a large number of genes ( n  = 316) correlated with mercury levels in TD but not in AU boys ( P  ≤ 0.05), the most represented biological functions being cell death and cell morphology. Expression of 189 genes correlated with mercury levels in AU but not in TD boys ( P  ≤ 0.05), the most represented biological functions being cell morphology, amino acid metabolism, and antigen presentation. These data and those in our companion study on correlation of gene expression and lead levels show that AU and TD children display different correlations between transcript levels and low levels of mercury and lead. These findings might suggest different genetic transcriptional programs associated with mercury in AU compared to TD children.