Tarquini Federica, Picchiassi Elena, Coata Giuliana, Centra Michela, Bini Vittorio, Meniconi Samanta, Antonelli Chiara, Giardina Irene, Di Renzo Gian Carlo
Laboratory of Prenatal Biochemistry and Molecular Biology, Department of Biomedical and Surgical Sciences, University of Perugia, 06132 Perugia, Italy.
Department of Internal Medicine, University of Perugia, 06132 Perugia, Italy.
Biomed Rep. 2018 Jul;9(1):81-89. doi: 10.3892/br.2018.1103. Epub 2018 May 29.
The purpose of the present study was to search for associations between spontaneous preterm birth (sPTB), single nucleotide polymorphisms (SNPs) associated with the apoptotic pathway as triggered by oxidative stress, maternal lifestyle and health status. SNP genotyping [rs7560 for c-Jun N-terminal kinase (JNK), rs9517320 for mammalian STE20-like protein kinase 3 (MST3), rs1049216 for caspase 3 (CASP3)] in the placenta and maternal blood of 300 controls with at-term birth and 43 cases of sPTB was performed. No association was identified in genotype frequencies or combinations of foetal/maternal genotypes between single SNPs and sPTB. The risk of sPTB was significantly reduced by physical activity and significantly increased by current hypertensive diseases, premature rupture of membranes (PROM) or preterm PROM (P-PROM) and previous sPTB. The TT/GA genotype of JNK/CASP3 in maternal blood and maternal health status (current hypertensive diseases, current PROM/P-PROM, previous sPTB) were independently associated with sPTB. The present findings suggested that, independently of other maternal factors, pregnant women carrying the TT/GA genotype of JNK/CASP3 were more susceptible to sPTB than women bearing the GT/GA (our reference) genotype; that the apoptotic pathway triggered by oxidative stress was involved; and that genetic and non-genetic factors contributed to sPTB. Knowledge of these aspects may aid to improve the management of pregnancies by indicating the lifestyle to be adopted on the basis of sPTB susceptibility.
本研究的目的是探寻自然早产(sPTB)、与氧化应激引发的凋亡途径相关的单核苷酸多态性(SNP)、孕产妇生活方式和健康状况之间的关联。对300例足月分娩对照者以及43例sPTB患者的胎盘和母血进行了SNP基因分型[针对c-Jun氨基末端激酶(JNK)的rs7560、针对哺乳动物STE20样蛋白激酶3(MST3)的rs9517320、针对半胱天冬酶3(CASP3)的rs1049216]。未发现单个SNP与sPTB之间在基因型频率或胎儿/母亲基因型组合方面存在关联。体育活动可显著降低sPTB风险,而当前的高血压疾病、胎膜早破(PROM)或早产胎膜早破(P-PROM)以及既往sPTB则会显著增加sPTB风险。母血中JNK/CASP3的TT/GA基因型与孕产妇健康状况(当前高血压疾病、当前PROM/P-PROM、既往sPTB)均与sPTB独立相关。本研究结果表明,独立于其他孕产妇因素,携带JNK/CASP3的TT/GA基因型的孕妇比携带GT/GA(我们的参照)基因型的孕妇更易发生sPTB;氧化应激引发的凋亡途径参与其中;遗传和非遗传因素均对sPTB有影响。了解这些方面可能有助于改善孕期管理,即根据sPTB易感性指明应采取的生活方式。