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

Stamova, Boryana; Green, Peter G.; Tian, Yingfang; Hertz‐Picciotto, Irva; Pessah, Isaac N.; Hansen, Robin; Yang, Xiaowei; Teng, Jennifer; Gregg, Jeffrey P.; Ashwood, Paul; Water, Judith A Van de; Sharp, Frank R.

doi:10.1007/s12640-009-9137-7

Cited by 53 publications

(35 citation statements)

References 96 publications

(125 reference statements)

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“…They found 11 genes whose expression correlated inversely with mercury levels in boys diagnosed with autism compared to typically developing children. One limitation of this study was that samples collected from children ages 2–5 do not consider the possible direct role of mercury as a causal factor for autism, which likely starts in utero or shortly after birth (Stamova et al, 2011). …”

Section: Peripheral Blood Gene Expression Studiesmentioning

confidence: 99%

Variation in Gene Expression in Autism Spectrum Disorders: An Extensive Review of Transcriptomic Studies

Ansel¹,

Rosenzweig²,

Zisman³

et al. 2017

Front. Neurosci.

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Autism spectrum disorders (ASDs) are a group of complex neurodevelopmental conditions that present in early childhood and have a current estimated prevalence of about 1 in 68 US children, 1 in 42 boys. ASDs are heterogeneous, and arise from epigenetic, genetic and environmental origins, yet, the exact etiology of ASDs still remains unknown. Individuals with ASDs are characterized by having deficits in social interaction, impaired communication and a range of stereotyped and repetitive behaviors. Currently, a diagnosis of ASD is based solely on behavioral assessments and phenotype. Hundreds of diverse ASD susceptibility genes have been identified, yet none of the mutations found account for more than a small subset of autism cases. Therefore, a genetic diagnosis is not yet possible for the majority of the ASD population. The susceptibility genes that have been identified are involved in a wide and varied range of biological functions. Since the genetics of ASDs is so diverse, information on genome function as provided by transcriptomic data is essential to further our understanding. Gene expression studies have been extremely useful in comparing groups of individuals with ASD and control samples in order to measure which genes (or group of genes) are dysregulated in the ASD group. Transcriptomic studies are essential as a key link between measuring protein levels and analyzing genetic information. This review of recent autism gene expression studies highlights genes that are expressed in the brain, immune system, and processes such as cell metabolism and embryology. Various biological processes have been shown to be implicated with ASD individuals as well as differences in gene expression levels between different types of biological tissues. Some studies use gene expression to attempt to separate autism into different subtypes. An updated list of genes shown to be significantly dysregulated in individuals with autism from all recent ASD expression studies will help further research isolate any patterns useful for diagnosis or understanding the mechanisms involved. The functional relevance of transcriptomic studies as a method of classifying and diagnosing ASD cannot be underestimated despite the possible limitations of transcriptomic studies.

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Section: Peripheral Blood Gene Expression Studiesmentioning

confidence: 99%

Variation in Gene Expression in Autism Spectrum Disorders: An Extensive Review of Transcriptomic Studies

Ansel¹,

Rosenzweig²,

Zisman³

et al. 2017

Front. Neurosci.

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show abstract

“…Two recent studies examined the correlation between gene transcription profiles (35,000+ genes) and heavy metal body burdens in children with autism and controls (Stamova, Green et al 2011; Tian, Green et al 2011). Mercury loads correlated with the expression of several immunologically relevant genes across all study participants.…”

Section: Environmental Factors In Autism and Immune Dysfunctionmentioning

confidence: 99%

Cytokine dysregulation in autism spectrum disorders (ASD): Possible role of the environment

Goines

Ashwood

2013

Neurotoxicology and Teratology

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261

177

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Autism spectrum disorders (ASD) are neurodevelopmental diseases that affect an alarming number of individuals. The etiological basis of ASD is unclear, and evidence suggests it involves both genetic and environmental factors. There are many reports of cytokine imbalances in ASD. These imbalances could have a pathogenic role, or they may be markers of underlying genetic and environmental influences. Cytokines act primarily as mediators of immunological activity, but they also have significant interactions with the nervous system. They participate in normal neural development and function, and inappropriate activity can have a variety of neurological implications. It is therefore possible that cytokine dysregulation contributes directly to neural dysfunction in ASD. Further, cytokine profiles change dramatically in the face of infection, disease, and toxic exposures. Therefore, imbalances may represent an immune response to environmental contributors to ASD. The following review is presented in two main parts. First, we discuss select cytokines implicated in ASD, including IL-1Β, IL-6, IL-4, IFN-γ, and TGF-Β, and focus on their role in the nervous system. Second, we explore several neurotoxic environmental factors that may be involved in the disorders, and focus on their immunological impacts. This review represents an emerging model that recognizes the importance of both genetic and environmental factors in ASD etiology. We propose that the immune system provides critical clues regarding the nature of the gene by environment interactions that underlie ASD pathophysiology.

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“…50 The observed increased expression of Gstp1, Prdx3 and Pdia4 may be induced by the oxidative stress conditions. In the case of Gstp1, its upregulation is consistent with our previous study carried out in vitro with HepG2 cells, 7 in which an increased GST activity was observed after 2 h of MeHg exposure and continued increasing up to 24 h. This increased GST activity could be related to the cellular detoxification of MeHg 41 since GST catalyses the reaction of endogenous GSH with xenobiotics to yield less toxic conjugates that are easily eliminated.…”

Section: Mehg Exposure Affects the Energy Production Machinerymentioning

confidence: 96%

Analysis of protein expression in developmental toxicity induced by MeHg in zebrafish

Cuello

Ximénez-Embún

Ruppen

et al. 2012

Analyst

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Mercury toxicity and its implications in development are a major concern, due to the major threat to ecosystems and human health that this compound represents. Although some of the effects of methylmercury (MeHg) exposure have been extensively studied, the molecular mechanisms of interaction between this compound and developing organisms are still not completely understood. To provide further insights into these mechanisms, we carried out a quantitative proteomic study (iTRAQ) using zebrafish larvae exposed to 5 μg L(-1) and 25 μg L(-1) MeHg as a model. In this study, a multidimensional approach combining isoelectric focusing (IEF) and strong cation exchange (SCX) followed by reversed phase liquid chromatography prior to MALDI TOF/TOF analysis was employed, which resulted in a substantial increase in proteome coverage. Among the proteins identified, 71 were found de-regulated by more than 1.5-fold, and implicated in embryonic development, protein synthesis, calcium homeostasis and energy production. Furthermore, morphological and histological analysis of exposed larvae was carried out, reflecting changes such as smaller swim bladder, remaining yolk, bent body axis and accumulation of blood in the heart, among others.

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

Cited by 53 publications

References 96 publications

Variation in Gene Expression in Autism Spectrum Disorders: An Extensive Review of Transcriptomic Studies

Variation in Gene Expression in Autism Spectrum Disorders: An Extensive Review of Transcriptomic Studies

Cytokine dysregulation in autism spectrum disorders (ASD): Possible role of the environment

Analysis of protein expression in developmental toxicity induced by MeHg in zebrafish

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