Abstract
Purpose
To investigate interactions on gestational age among two environmental risk factors and four maternal genetic polymorphisms: organic solvents, passive smoking, CYP1A1 rs4646903 (MspI), EPHX1 rs2234922 (His139Arg), GSTT1 and PON2 rs12026 (Ala148Gly).
Methods
A pregnant women cohort was conducted at Beijing Yanshan Petrochemical Corporation, and 1,097 mothers with live singleton births were included in analysis. Generalized Multifactor Dimensionality Reduction (GMDR) method was used to explore interactions among these factors with adjustment for important potential confounders. Multiple linear regression models were used to estimate the association of interaction with gestational age.
Results
A three-factor model of organic solvents, GSTT1 and PON2 rs12026 had the highest testing balanced accuracy (57.05 %) and best cross-validation consistency (10/10). Compared with organic solvents unexposed mothers with GSTT1 non-null genotype and PON2 rs12026 CC genotype, organic solvents exposed mothers with GSTT1 null genotype and PON2 rs12026 CG + GG genotype had the largest reduction in gestational age (−0.36 weeks, 95%CI: −0.70 to −0.02). The significant reductions in different groups were from 0.24 weeks to 0.36 weeks.
Conclusions
Maternal genetic susceptibility GSTT1 and PON2 rs12026 could significantly modify the association of organic solvents with gestational age.
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Abbreviations
- CI:
-
confidence interval
- CYP1A1:
-
cytochrome P-450 1A1
- EPHX1:
-
epoxide hydrolase 1
- GMDR:
-
generalized multifactor dimensionality reduction
- GSTT1:
-
glutathione S-transferase theta-1
- hCG:
-
human chorionic gonadotrophin
- OSHA:
-
Occupational Safety and Health Administration
- PON2:
-
paraoxonase2
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Acknowledgment
We sincerely thank all of the participants and their families for participating in this study, and we gratefully acknowledge the invaluable assistance of clinical, field and laboratory staff who contributed to making this work possible. This study is supported in part by grants R825818 from the Environmental Protection Agency, 1R01 HD32505-01 from the National Institute of Child Health and Human Development, 1R01 ES08337-01 from the National Institute of Environmental Health Science and 1R01 OH03027 from the National Institute of Occupational Safety and Health.
Ethical issue
This study was approved by the ethics committee of Peking University Health Science Center.
All participants gave their informed content prior to participating in this study.
Conflict of interest
The authors declare that they have no conflict of interest.
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Capsule Organic solvents exposure and maternal genetic variants: GSTT1 and PON2 rs12026 have an interaction on gestational age in Chinese women.
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Li, S., Fang, K., Wang, W. et al. Gene-environment interaction among GSTT1, PON2 polymorphisms and organic solvents on gestational age in a Chinese women cohort. J Assist Reprod Genet 31, 881–888 (2014). https://doi.org/10.1007/s10815-014-0256-6
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DOI: https://doi.org/10.1007/s10815-014-0256-6