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Influence of genetic polymorphisms on arsenic methylation efficiency during pregnancy: Evidence from a Spanish birth cohort

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Influence of genetic polymorphisms on arsenic methylation efficiency during pregnancy: Evidence from a Spanish birth cohort

dc.contributor.author	Ballester Díez, Ferran
dc.contributor.author	Soler Blasco, Raquel
dc.contributor.author	Harari, Florencia
dc.contributor.author	Riutort Mayol, Gabriel
dc.contributor.author	Murcia Hinarejos, Mario
dc.contributor.author	Lozano, Manuel
dc.contributor.author	Irizar, Amaia
dc.contributor.author	Santa-Marina, Loreto
dc.contributor.author	Zubero, Miren Begoña
dc.contributor.author	Fernández Jiménez, Nora
dc.contributor.author	Braeuer, Simone
dc.contributor.author	Llop Pérez, Sabrina
dc.date.accessioned	2023-11-02T08:02:03Z
dc.date.available	2023-11-03T05:45:06Z
dc.date.issued	2023	es_ES
dc.identifier.uri	https://hdl.handle.net/10550/90781
dc.description.abstract	Background: Inorganic arsenic (iAs) is a widespread toxic metalloid. It is well-known that iAs metabolism and its toxicity are mediated by polymorphisms in AS3MT and other genes. However, studies during pregnancy are scarce. We aimed to examine the role of genetic polymorphisms in AS3MT, GSTO2, N6AMT1, MTHFR, MTR, FTCD, CBS, and FOLH1 in iAs methylation efficiency during pregnancy. Methods: The study included 541 pregnant participants from the INMA (Environment and Childhood) Spanish cohort. Using high-performance liquid chromatography coupled to inductively coupled plasma-tandem mass, we measured arsenic (iAs and the metabolites monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)) in urine samples collected during the first trimester. iAs methylation efficiency was determined based on relative concentrations of the As metabolites in urine (%MMA, %DMA, and %iAs). Thirty-two single nucleotide polymorphisms (SNPs) in nine genes were determined in maternal DNA; AS3MT haplotypes were inferred. We assessed the association between genotypes/haplotypes and maternal As methylation efficiency using multivariate linear regression models. Results: The median %MMA and %DMA were 5.3 %, and 89 %, respectively. Ancestral alleles of AS3MT SNPs (rs3740393, rs3740390, rs11191453, and rs11191454) were significantly associated with higher %MMA, %iAs, and lower %DMA. Pregnant participants with zero copies of the GGCTTCAC AS3MT haplotype presented a higher %MMA. Statistically significant associations were also found for the FOLH1 SNP rs202676 (β 0.89 95%CI: 0.24, 1.55 for carriers of the G allele vs. the A allele). Conclusions: Our study shows that ancestral alleles in AS3MT polymorphisms were associated with lower As methylation efficiency in early pregnancy and suggests that FOLH1 also plays a role in As methylation efficiency. These results support the hypothesis that As metabolism is multigenic, being a key element for identifying susceptible populations.	es_ES
dc.language.iso	en	es_ES
dc.publisher	Elsevier	es_ES
dc.source	Soler-Blasco R, Harari F, Riutort-Mayol G, Murcia M, Lozano M, Irizar A, Marina LS, Zubero MB, Fernández-Jimenez N, Braeuer S, Ballester F, Llop S. Influence of genetic polymorphisms on arsenic methylation efficiency during pregnancy: Evidence from a Spanish birth cohort. Sci Total Environ. 2023 Nov 20;900:165740. doi: 10.1016/j.scitotenv.2023.165740. Epub 2023 Jul 24. PMID: 37495132.	es_ES
dc.subject	arsénico	es_ES
dc.subject	exposición prenatal	es_ES
dc.subject	genètica	es_ES
dc.title	Influence of genetic polymorphisms on arsenic methylation efficiency during pregnancy: Evidence from a Spanish birth cohort	es_ES
dc.type	journal article	es_ES
dc.subject.unesco	UNESCO::CIENCIAS MÉDICAS	es_ES
dc.identifier.doi	10.1016/j.scitotenv.2023.165740	es_ES
dc.accrualmethod	BS	es_ES
dc.embargo.terms	0 days	es_ES
dc.type.hasVersion	VoR	es_ES
dc.rights.accessRights	open access	es_ES