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Assessment of Maternal Vascular Remodeling During Pregnancy in the Mouse Uterus
Published on: December 5, 2015
Gene-environment interaction and maternal arsenic methylation efficiency during pregnancy
Shangzhi Gao1, Md Golam Mostofa2, Quazi Quamruzzaman2
1Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Single nucleotide polymorphisms (SNPs) influence arsenic metabolism in pregnant women, but gene-environment interactions showed limited effects. Arsenic methylation efficiency varied based on specific As3MT gene variants, with some associations not replicating previous findings.
Area of Science:
- Environmental Health
- Genetics
- Toxicology
Background:
- Single nucleotide polymorphisms (SNPs) may impact arsenic methylation efficiency and metabolism.
- Gene-environment interactions' role in arsenic metabolism during pregnancy is not well understood.
- Understanding these interactions is crucial for assessing pregnancy outcomes.
Purpose of the Study:
- Investigate the main effects of SNPs on arsenic methylation efficiency in pregnant women.
- Examine potential interactions between SNPs and arsenic exposure.
- Assess the implications for arsenic metabolism during pregnancy.
Main Methods:
- Recruited 1613 pregnant women in Bangladesh.
- Collected urine samples at two time points to measure arsenic metabolites (iAs%, MMA%, DMA%).
- Genotyped 63 candidate SNPs in genes like As3MT, N6AMT1, and GSTO2.
- Used linear regression to analyze SNP associations and SNP-arsenic interactions.
Main Results:
- Intron variants in As3MT were associated with dimethylarsinic acid (DMA%) levels.
- Specific SNPs (e.g., rs9527, rs1046778, rs3740393) showed associations with DMA% at different gestational periods.
- Polymorphisms in As3MT, GSTO2, and N6AMT1 exhibited varied effect sizes on DMA%.
- No statistically significant SNP-arsenic interactions were found after FDR adjustment.
- As3MT and As3MT/CNNM2 haplotypes were associated with DMA%.
Conclusions:
- Not all previously reported genetic associations with arsenic methylation efficiency were replicated in this pregnant population.
- Arsenic exposure levels had a limited effect on modifying the relationship between genetic variations and arsenic methylation efficiency.
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