Correlations of Gene Expression with Blood Lead Levels in Children with Autism Compared to Typically Developing Controls

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

doi:10.1007/s12640-009-9126-x

Cited by 58 publications

(53 citation statements)

References 64 publications

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“…Studies with moderate maternal blood cadmium levels (B‐Cd; below a suggested reference value of 1 μg/L11) and adjustment for smoking have generally found no associations with birthweight, birth length, head circumference or preterm delivery,8, 12, 13 but other studies have found negative associations particularly with birthweight14, 15, 16 (Table S1). Even where exposure levels are higher and effects could potentially be more evident, again some studies have found no associations with birth outcomes,10, 17 while others have found adverse associations 18. It has recently been suggested that adverse events associated with maternal Cd exposure are sex‐specific, with effects on birthweight and birth length being more severe in or confined to girls8, 19, 20, 21 and that this might mask effects in mixed‐sex studies.…”

mentioning

confidence: 99%

Moderate Prenatal Cadmium Exposure and Adverse Birth Outcomes: a Role for Sex‐Specific Differences?

Taylor

Golding

Emond

2016

Paediatric Perinatal Epid

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Background/AimStudies on the effects of moderate prenatal exposure to cadmium (Cd) on birth outcomes have been contradictory and it has been suggested that effects may be partly masked by sex‐specific effects. Our aim was to examine the association of Cd exposure in a large group of pregnant women with birth outcomes in the whole group of participants and by sex.MethodsPregnant women were enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC). Whole blood samples for singleton pregnancies with a live birth were analysed for Cd (n = 4191). Data collected on the infants included anthropometric variables and gestational age at delivery. Data were analysed using SPSS v18.ResultsThere were adverse associations of maternal blood Cd level with birthweight (unstandardized B coefficient −62.7 g, 95% CI −107.0, −18.4) and crown–heel length (−0.28 cm, 95% CI −0.48, −0.07) in adjusted regression models. On stratification by sex, maternal blood Cd level was adversely associated with birthweight (−87.1 g, 95% CI −144.8, −29.4), head circumference (−0.22 cm, 95% CI −0.39, −0.04), and crown–heel length (−0.44 cm, 95% CI −0.71, −0.18) in girls but not in boys in adjusted regression models.ConclusionIn these pregnant women with moderate prenatal Cd exposure there evidence of adverse associations with birth anthropometry variables in the whole group. However, there was evidence of associations with anthropometric variables in girls that were not evident in boys. Sex‐specific effects require further investigation in large cohorts as a possible contributor to the lack of associations generally found in mixed‐sex studies.

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mentioning

confidence: 99%

Moderate Prenatal Cadmium Exposure and Adverse Birth Outcomes: a Role for Sex‐Specific Differences?

Taylor

Golding

Emond

2016

Paediatric Perinatal Epid

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“…There are conflicting reports regarding lead in autism. A few studies have documented higher serum lead levels [214] often associated with pica [215], although more recent studies show no difference between autism and control populations [216,217]. Association between mercury levels and autism is also somewhat contradictory [218].…”

Section: Toxic Exposures Teratogens and Medicationsmentioning

confidence: 99%

The Genetic and Epigenetic Basis Involved in the Pathophysiology of ASD: Therapeutic Implications

Carrascosa-Romero¹,

Cabo²

2017

Autism - Paradigms, Recent Research and Clinical Applications

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The prevalence of autism has increased in an exponential way in the past few years. Many monogenetic mutations as well as copy number variants and single nucleotide polymorphisms have been associated with autism spectrum disorders (ASD), a large proportion of which occur in genes associated with synaptogenesis and synaptic function. However, the increase in appearance of genetic alterations does not explain the etiology of an elevated number of ASD cases. Recent research is now focusing on the role of environmental/epigenetic factors, which by themselves and/or in combination with classical genetic factors, may be the root cause of a large number of ASDs. In this chapter we review the current literature regarding the epigenetic changes involved in ASD, including their possible mechanisms of action such as oxidative stress, altered fatty acid metabolism, mitochondrial dysfunction, DNA methylation and histone methylation (via the one-carbon metabolism cycle), histone variants, and ATP-dependent chromatin remodeling. We discuss possible new biochemical markers related to autism as well as new lines of research for therapeutic targets.

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“…Two of these, NOTCH1 resp. ITGB3, are also known as genes that are responsive to PCBs and cadmium chloride exposure in rodents, respectively to lead in humans (21)(22)(23).…”

Section: Relevant Genesmentioning

confidence: 99%

“…It plays an important role in cell growth and developmental processes by modulating expression of particular genes. High expression levels of this gene have Tian (23).…”

Section: 40mentioning

confidence: 99%

Distinct genotype-dependent differences in transcriptome responses in humans exposed to environmental carcinogens

Espín-Pérez¹,

Kok²,

Jennen³

et al. 2015

CARCIN

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Considering genetic variability in population studies focusing on the health risk assessment of exposure to environmental carcinogens may provide improved insights in individual environmental cancer risks. Therefore, the current study aims to determine the impact of genetic polymorphisms on the relationship between exposure and gene expression, by identifying exposure-dependently coregulated genes and genetic pathways. Statistical analysis based on mixed models, was performed to relate gene expression data from 134 subjects to exposure measurements of multiple carcinogens, 28 polymorphisms, age, sex and biomarkers of cancer risk. We evaluated the combined exposure to cadmium, lead, polychlorinated biphenyls, p,p′-dichlorodiphenyldichloroethylene, hexachlorobenzene and 1-OH-pyrene, and the outcome was biologically interpreted by using ConsensusPathDB, thereby focusing on carcinogenesis-related pathways. We found generic and carcinogenesisrelated pathways deregulated in both sexes, but males showed a stronger transcriptome response than females. We highlighted NOTCH1, CBR1, ITGB3, ITGA4, ADI1, HES1, NCOA2 and SMARCA2 in view of their direct link with cancer development. Two of these, NOTCH1 and ITGB3, are also known to respond to PCBs and cadmium chloride exposure in rodents and to lead in humans. Subjects carrying a high number of risk alleles appear more responsive to combined carcinogen exposure with respect to the induced expression of some of these cancer-related genes, which may be indicative of increased cancer risk as a consequence of environmental factors.

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Correlations of Gene Expression with Blood Lead Levels in Children with Autism Compared to Typically Developing Controls

Cited by 58 publications

References 64 publications

Moderate Prenatal Cadmium Exposure and Adverse Birth Outcomes: a Role for Sex‐Specific Differences?

Moderate Prenatal Cadmium Exposure and Adverse Birth Outcomes: a Role for Sex‐Specific Differences?

The Genetic and Epigenetic Basis Involved in the Pathophysiology of ASD: Therapeutic Implications

Distinct genotype-dependent differences in transcriptome responses in humans exposed to environmental carcinogens

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