摘要
Objective This study aimed to assess the associations between maternal drug use,cytochrome P450(CYP450)genetic polymorphisms,and their interactions with the risk of congenital heart defects(CHDs)in offspring.Methods A case-control study involving 569 mothers of CHD cases and 652 controls was conducted from November 2017 to January 2020.Results After adjusting for potential confounding factors,the results show that mothers who used ovulatory drugs(adjusted odds ratio[a OR]=2.12;95% confidence interval[CI]:1.08-4.16),antidepressants(a OR=2.56;95%CI:1.36-4.82),antiabortifacients(a OR=1.55;95%CI:1.00-2.40),or traditional Chinese drugs(a OR=1.97;95%CI:1.26-3.09)during pregnancy were at a significantly higher risk of CHDs in offspring.Maternal CYP450 genetic polymorphisms at rs1065852(A/T vs.A/A:OR=1.53,95%CI:1.10-2.14;T/T vs.A/A:OR=1.57,95%CI:1.07-2.31)and rs16947(G/G vs.C/C:OR=3.41,95%CI:1.82-6.39)were also significantly associated with the risk of CHDs in offspring.Additionally,significant interactions were observed between the CYP450 genetic variants and drug use on the development of CHDs.Conclusions In those of Chinese descent,ovulatory drugs,antidepressants,antiabortifacients,and traditional Chinese medicines may be associated with the risk of CHDs in offspring.Maternal CYP450 genes may regulate the effects of maternal drug exposure on fetal heart development.
基金
supported by the National Natural Science Foundation Program of China[82073653,81803313,and 81974019]
China Postdoctoral Science Foundation[2020M682644]
Hunan Provincial Science and Technology Talent Support Project(2020TJ-N07)
Natural Science Foundation of Hunan Province[2018JJ2551]
Hunan Provincial Key Research and Development Program[2018SK2063 and 2018SK2062]
Open Project from NHC Key Laboratory of Birth Defect for Research and Prevention[KF2020006]
National Key Research and Development Program of China[2018YFA0108700 and2017YFA0105602]
Postgraduate Scientific Research Innovation Project of Hunan Province[grant number CX20200271]
Fundamental Research Funds for the Central Universities of Central South University[grant number 2020zzts798]。