Daud Aizati N A, Bergman Jorieke E H, Kerstjens-Frederikse Wilhelmina S, van der Vlies Pieter, Hak Eelko, Berger Rolf M F, Groen Henk, Wilffert Bob
Unit of PharmacoTherapy, -Epidemiology & -Economics, Department of Pharmacy, University of Groningen, Groningen Research Institute of Pharmacy, Groningen, The Netherlands.
School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia.
Pharmacogenomics. 2017 Jul;18(10):987-1001. doi: 10.2217/pgs-2017-0036. Epub 2017 Jun 22.
To explore the role of pharmacogenetics in determining the risk of congenital heart anomalies (CHA) with prenatal use of serotonin reuptake inhibitors.
We included 33 case-mother dyads and 2 mother-only (child deceased) cases of CHA in a case-only study. Ten genes important in determining fetal exposure to serotonin reuptake inhibitors were examined: CYP1A2, CYP2C9, CYP2C19, CYP2D6, ABCB1, SLC6A4, HTR1A, HTR1B, HTR2A and HTR3B.
Among the exposed cases, polymorphisms that tended to be associated with an increased risk of CHA were SLC6A4 5-HTTLPR and 5-HTTVNTR, HTR1A rs1364043, HTR1B rs6296 and rs6298 and HTR3B rs1176744, but none reached statistical significance due to our limited sample sizes.
We identified several polymorphisms that might potentially affect the risk of CHA among exposed fetuses, which warrants further investigation.
探讨药物遗传学在确定产前使用5-羟色胺再摄取抑制剂时先天性心脏异常（CHA）风险中的作用。
在一项病例对照研究中，我们纳入了33例病例-母亲二元组以及2例仅母亲（孩子已死亡）的CHA病例。检测了在确定胎儿暴露于5-羟色胺再摄取抑制剂中起重要作用的10个基因：CYP1A2、CYP2C9、CYP2C19、CYP2D6、ABCB1、SLC6A4、HTR1A、HTR1B、HTR2A和HTR3B。
在暴露病例中，倾向于与CHA风险增加相关的多态性有SLC6A4 5-HTTLPR和5-HTTVNTR、HTR1A rs1364043、HTR1B rs6296和rs6298以及HTR3B rs1176744，但由于样本量有限，均未达到统计学显著性。
我们确定了几种可能潜在影响暴露胎儿CHA风险的多态性，这值得进一步研究。
