Association of maternal prenatal phthalate exposure and genetic polymorphisms of metabolic enzyme genes with spontaneous preterm birth: a nested case-control study in China.

Abstract

Background: The relationship between prenatal phthalate exposure and preterm birth from previous studies has been inconsistent. Meanwhile, few studies have explored the relationship between spontaneous preterm birth (SPTB) and genetic polymorphisms of metabolic enzyme genes or gene-phthalate interactions. The aim of this study is to evaluate the association of maternal phthalate exposure, genetic polymorphisms, and their interactions with SPTB.

Methods: A total of 182 cases with SPTB and 321 controls with full-term delivery were enrolled. Nine phthalate metabolites in maternal second trimester urine samples were measured by ultra-high performance liquid chromatography coupled with tandem mass spectrometry. Genotyping was performed on twenty-six single nucleotide polymorphisms (SNPs) of metabolic enzyme genes, including CYP2C9, CYP2C19, UGT1A7, UGT2B7 and UGT2B15 genes. The associations between maternal phthalate exposure or genetic polymorphisms and SPTB were estimated by multivariable logistic regression analysis. The impact of interactions between gene-gene and gene-phthalate exposure on SPTB were analyzed via generalized multifactor dimensionality reduction.

Results: There were no significant differences in the concentrations of phthalate metabolites between the two groups. No statistically significant associations were observed between maternal phthalate exposure and SPTB. The rs4244285 polymorphism of CYP2C19 gene was associated with decreased odds of SPTB under the log-additive (aOR = 0.73, 95% CI: 0.55-0.98) and recessive model (aOR = 0.37, 95% CI: 0.18-0.74). Two SNP loci of UGT2B15 were associated with increased odds of SPTB under the recessive genetic model (aOR = 3.85, 95% CI: 1.31-11.35 for rs3100, and aOR = 3.85, 95% CI: 1.31-11.35 for rs4148269). However, these associations were not significant after the false discovery rate correction. No significant gene-gene or gene-phthalate metabolites interactions for SPTB were observed.

Conclusions: Maternal phthalate exposure in the present subjects and genetic polymorphisms of metabolic enzyme genes were not associated with SPTB. Moreover, there were no significant gene-gene or gene-phthalates interactions for SPTB.