Department of Neurology, University of California at Davis Medical Center, Sacramento, CA 95817, USA.
Neurotox Res. 2011 Jan;19(1):31-48. doi: 10.1007/s12640-009-9137-7. Epub 2009 Nov 24.
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.
血液中的基因表达与自闭症（AU）2-5 岁男孩与年龄匹配的正常发育（TD）对照组男孩的血液汞水平相关。这样做是为了研究两组男孩是否可能以不同的方式代谢有毒物质，如汞。从血液中分离出 RNA，并在全基因组 Affymetrix Human U133 表达微阵列上评估基因表达。使用电感耦合等离子体质谱仪测量汞水平。进行协方差分析（ANCOVA），并在校正年龄和批次效应后，计算基因表达与汞水平之间的部分相关。为了减少假阳性，仅分析了通过 ANCOVA 模型共享的基因。在与 AU 和 TD 男孩的汞水平相关的 26 个基因中，有 11 个在两组之间存在显著差异（P（诊断*汞）≤0.05）。大量基因（n=316）的表达与 TD 男孩的汞水平相关，但与 AU 男孩的表达不相关（P≤0.05），最具代表性的生物学功能是细胞死亡和细胞形态。189 个基因的表达与 AU 男孩的汞水平相关，但与 TD 男孩的表达不相关（P≤0.05），最具代表性的生物学功能是细胞形态、氨基酸代谢和抗原呈递。这些数据以及我们关于基因表达与铅水平相关性的研究表明，AU 和 TD 儿童的转录水平与低水平汞和铅之间的相关性不同。这些发现可能表明与 AU 儿童相比，汞与不同的遗传转录程序相关。
