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Polymorphisms in maternal folate pathway genes interact with arsenic in drinking water to influence risk of myelomeningocele.

ABSTRACT: Arsenic induces neural tube defects in many animal models. Additionally, studies have shown that mice with specific genetic defects in folate metabolism and transport are more susceptible to arsenic-induced neural tube defects. We sought to determine whether 14 single-nucleotide polymorphisms in genes involved in folate metabolism modified the effect of exposure to drinking water contaminated with inorganic arsenic and posterior neural tube defect (myelomeningocele) risk.Fifty-four mothers of children with myelomeningocele and 55 controls were enrolled through clinical sites in rural Bangladesh in a case-control study of the association between environmental arsenic exposure and risk of myelomeningocele. We assessed participants for level of myelomeningocele, administered questionnaires, conducted biological and environmental sample collection, and performed genotyping. Inductively coupled plasma mass spectrometry was used to measure inorganic arsenic concentration in drinking water. Candidate single-nucleotide polymorphisms were identified through review of the literature.Drinking water inorganic arsenic concentration was associated with increased risk of myelomeningocele for participants with 4 of the 14 studied single-nucleotide polymorphisms in genes involved in folate metabolism: the AA/AG genotype of rs2236225 (MTHFD1), the GG genotype of rs1051266 (SLC19A1), the TT genotype of rs7560488 (DNMT3A), and the GG genotype of rs3740393 (AS3MT) with adjusted odds ratio of 1.13, 1.31, 1.20, and 1.25 for rs2236225, rs1051266, rs7560488, and rs3740393, respectively.Our results support the hypothesis that environmental arsenic exposure increases the risk of myelomeningocele by means of interaction with folate metabolic pathways.

SUBMITTER: Mazumdar M

PROVIDER: S-EPMC4565773 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Polymorphisms in maternal folate pathway genes interact with arsenic in drinking water to influence risk of myelomeningocele.

Mazumdar Maitreyi M Valeri Linda L Rodrigues Ema G EG Ibne Hasan Md Omar Sharif MO Hamid Rezina R Paul Ligi L Selhub Jacob J Silva Fareesa F Mostofa Md Golam MG Quamruzzaman Quazi Q Rahman Mahmuder M Christiani David C DC

Birth defects research. Part A, Clinical and molecular teratology 20150806 9

<h4>Background</h4>Arsenic induces neural tube defects in many animal models. Additionally, studies have shown that mice with specific genetic defects in folate metabolism and transport are more susceptible to arsenic-induced neural tube defects. We sought to determine whether 14 single-nucleotide polymorphisms in genes involved in folate metabolism modified the effect of exposure to drinking water contaminated with inorganic arsenic and posterior neural tube defect (myelomeningocele) risk.<h4>M ...[more]

PMID: 26250961

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Project description:Arsenic contamination of drinking water is a serious public health threat. In Bangladesh, eight major safe water options provide an alternative to contaminated shallow tubewells: piped water supply, deep tubewells, pond sand filters, community arsenic-removal, household arsenic removal, dug wells, well-sharing, and rainwater harvesting. However, it is uncertain how well these options are accepted and used by the at-risk population. Based on the RANAS model (risk, attitudes, norms, ability, and self-regulation) this study aimed to identify the acceptance and use of available safe water options. Cross-sectional face-to-face interviews were used to survey 1,268 households in Bangladesh in November 2009 (n = 872), and December 2010 (n = 396). The questionnaire assessed water consumption, acceptance factors from the RANAS model, and socioeconomic factors. Although all respondents had access to at least one arsenic-safe drinking water option, only 62.1% of participants were currently using these alternatives. The most regularly used options were household arsenic removal filters (92.9%) and piped water supply (85.6%). However, the former result may be positively biased due to high refusal rates of household filter owners. The least used option was household rainwater harvesting (36.6%). Those who reported not using an arsenic-safe source differed in terms of numerous acceptance factors from those who reported using arsenic-safe sources: non-users were characterized by greater vulnerability; showed less preference for the taste and temperature of alternative sources; found collecting safe water quite time-consuming; had lower levels of social norms, self-efficacy, and coping planning; and demonstrated lower levels of commitment to collecting safe water. Acceptance was particularly high for piped water supplies and deep tubewells, whereas dug wells and well-sharing were the least accepted sources. Intervention strategies were derived from the results in order to increase the acceptance and use of each arsenic-safe water option.

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Polymorphisms in maternal folate pathway genes interact with arsenic in drinking water to influence risk of myelomeningocele.

Publications

Polymorphisms in maternal folate pathway genes interact with arsenic in drinking water to influence risk of myelomeningocele.

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