Polymorphisms in ATP-binding cassette transporters associated with maternal methylmercury disposition and infant neurodevelopment in mother-infant pairs in the Seychelles Child Development Study

Engström, Karin; Love, Tanzy; Watson, Gene E.; Zaręba, Grażyna; Yeates, Alison J.; Wahlberg, Karin; Alhamdow, Ayman; Thurston, Sally W.; Mulhern, Maria S.; McSorley, Emeir M.; Strain, JJ; Davidson, Philip W.; Shamlaye, Conrad; Myers, Gary J.; Rand, Matthew D.; Wijngaarden, Edwin van; Broberg, Karin

doi:10.1016/j.envint.2016.05.027

Cited by 32 publications

(22 citation statements)

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“…Epigenetic regulation is an important mechanism for modifying gene expression (Wang et al, ). As an important part of epigenetics, miRNAs play a vital role in regulation of transporter gene expression through binding the 3′‐UTR of genes (Koturbash et al, ; Wan et al, ; Engstrom et al, ; Kap et al, ).…”

Section: Discussionmentioning

confidence: 99%

A functional SNP in the 3′‐UTR of TAP2 gene interacts with microRNA hsa‐miR‐1270 to suppress the gene expression

Knox

Wang

Rogers

et al. 2017

Environ and Mol Mutagen

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The transporter associated with antigen processing 2 (TAP2) is involved in the development of multidrug resistance and the etiology of immunological diseases. In this study, we investigated whether the expression of TAP2 can be perturbed by single nucleotide polymorphisms (SNPs) located in 3′-untranslated region (3′-UTR) of the gene via interactions with microRNAs. Using a series of in silico assays, we selected the candidate microRNAs (miRNAs) with the potential to interact with functional SNPs of TAP2. The SNP rs241456—located in the 3′-UTR of TAP2—resides in a potential binding site for hsa-miR-1270 and hsa-miR-620. HEK 293 cells, from a human kidney cell line, were used to characterize the extent of binding of miRNAs to each polymorphic allele of the SNP by a luciferase reporter gene assay. RNA electrophoretic mobility shift assays were used to evaluate the interaction between the miRNAs and each allele sequence of the SNP. We found that hsa-miR-1270 inhibited luciferase activity by binding to the T allele of the SNP in an allele-specific manner. A negative correlation was also found between the expression of hsa-miR-1270 and the T allele of the SNP in kidney tissues. Our findings support the hypothesis that hsa-miR-1270 suppresses the production of TAP2 by binding to this SNP in the 3′-UTR of this gene.

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Section: Discussionmentioning

confidence: 99%

A functional SNP in the 3′‐UTR of TAP2 gene interacts with microRNA hsa‐miR‐1270 to suppress the gene expression

Knox

Wang

Rogers

et al. 2017

Environ and Mol Mutagen

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“…Some of these active transporters may also influence both inorganic and organic Hg uptake, distribution, and elimination at molecular level, modulating the cellular Hg efflux [ 5 , 41 , 42 ].…”

Section: Gene Classes Of Interest and Related Polymorphismsmentioning

confidence: 99%

“…Finally, attention must be drawn on the very recent study by Engström et al [ 41 ], based on a mother-child cohort from the Seychelles, a typically population suggestive of high fish intake and hair Hg concentrations. The authors identified in additional ABCC1 SNPs (rs215088, rs11075290, rs212093), ABCC2 (rs717620), and ABCB1 (rs2032582, rs1202169, rs10276499) some probable susceptibility markers to modulate the MeHg transport, distribution and elimination, based on the strong association of their genotypes with maternal hair Hg concentrations.…”

Section: Gene Classes Of Interest and Related Polymorphismsmentioning

confidence: 99%

“…The authors identified in additional ABCC1 SNPs (rs215088, rs11075290, rs212093), ABCC2 (rs717620), and ABCB1 (rs2032582, rs1202169, rs10276499) some probable susceptibility markers to modulate the MeHg transport, distribution and elimination, based on the strong association of their genotypes with maternal hair Hg concentrations. Among them, only the first aforementioned ABCC1 intronic variant, located in a promoter-flanking region, also showed adverse association with neurodevelopmental outcomes in children [ 41 ].…”

Section: Gene Classes Of Interest and Related Polymorphismsmentioning

confidence: 99%

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Genetic Aspects of Susceptibility to Mercury Toxicity: An Overview

Andreoli

Sprovieri

2017

IJERPH

120

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Human exposure to mercury is still a major public health concern. In this context, children have a higher susceptibility to adverse neurological mercury effects, compared to adults with similar exposures. Moreover, there exists a marked variability of personal response to detrimental mercury action, in particular among population groups with significant mercury exposure. New scientific evidence on genetic backgrounds has raised the issue of whether candidate susceptibility genes can make certain individuals more or less vulnerable to mercury toxicity. In this review, the aim is to evaluate a new genetic dimension and its involvement in mercury risk assessment, focusing on the important role played by relevant polymorphisms, located in attractive gene targets for mercury toxicity. Existing original articles on epidemiologic research which report a direct link between the genetic basis of personal vulnerability and different mercury repercussions on human health will be reviewed. Based on this evidence, a careful evaluation of the significant markers of susceptibility will be suggested, in order to obtain a powerful positive “feedback” to improve the quality of life. Large consortia of studies with clear phenotypic assessments will help clarify the “window of susceptibility” in the human health risks due to mercury exposure.

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“…Candidate genes in the glutathione (GSH) metabolism pathway have been primarily considered since the formation of MeHg-GSH conjugates are thought to be key to excretion (Ballatori and Clarkson, 1983; Barcelos et al, 2013; Custodio et al, 2004; Engström et al, 2008; Engström et al, 2016; Gundacker et al, 2007). However, results have been inconsistent regarding the modifying role of these genes.…”

Section: Introductionmentioning

confidence: 99%

CYP3A genes and the association between prenatal methylmercury exposure and neurodevelopment

Llop

Tran

Ballester

et al. 2017

Environment International

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Background Results on the association between prenatal exposure to methylmercury (MeHg) and child neuropsychological development are heterogeneous. Underlying genetic differences across study populations could contribute to this varied response to MeHg. Studies in Drosophila have identified the cytochrome p450 3A (CYP3A) family as candidate MeHg susceptibility genes. Objectives We evaluated whether genetic variation in CYP3A genes influences the association between prenatal exposure to MeHg and child neuropsychological development. Methods The study population included 2639 children from three birth cohort studies: two subcohorts in Seychelles (SCDS) (n =1160, 20 and 30 months of age, studied during the years 2001–2012), two subcohorts from Spain (INMA) (n=625, 14 months of age, 2003–2009), and two subcohorts from Italy and Greece (PHIME) (n=854, 18 months of age, 2006–2011). Total mercury, as a surrogate of MeHg, was analysed in maternal hair and/or cord blood samples. Neuropsychological development was evaluated using Bayley Scales of Infant Development (BSID). Three functional polymorphisms in the CYP3A family were analysed: rs2257401 (CYP3A7), rs776746 (CYP3A5), and rs2740574 (CYP3A4). Results There was no association between CYP3A polymorphisms and cord mercury concentrations. The scores for the BSID mental scale improved with increasing cord blood mercury concentrations for carriers of the most active alleles (β[95%CI]:=2.9[1.53,4.27] for CYP3A7 rs2257401 GG+GC, 2.51[1.04,3.98] for CYP3A5 rs776746 AA+AG and 2.31[0.12,4.50] for CYP3A4 rs2740574 GG+AG). This association was near the null for CYP3A7 CC, CYP3A5 GG and CYP3A4 AA genotypes. The interaction between the CYP3A genes and total mercury was significant (p<0.05) in European cohorts only. Conclusions Our results suggest that the polymorphisms in CYP3A genes may modify the response to dietary MeHg exposure during early life development.

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Polymorphisms in ATP-binding cassette transporters associated with maternal methylmercury disposition and infant neurodevelopment in mother-infant pairs in the Seychelles Child Development Study

Cited by 32 publications

References 25 publications

A functional SNP in the 3′‐UTR of TAP2 gene interacts with microRNA hsa‐miR‐1270 to suppress the gene expression

A functional SNP in the 3′‐UTR of TAP2 gene interacts with microRNA hsa‐miR‐1270 to suppress the gene expression

Genetic Aspects of Susceptibility to Mercury Toxicity: An Overview

CYP3A genes and the association between prenatal methylmercury exposure and neurodevelopment

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