子痫前期患者脂蛋白脂酶基因多态性对血脂及血脂比值的影响

The study on changes of lipid profiles and ratios and on relationships between polymorphism of lipoprotein lipase and pre-eclampsia

目的研究正常妊娠女性与子痫前期患者脂蛋白脂酶(lipoprotein lipase,LPL)基因S447X、N291S位点多态性对母体及新生儿血脂和血脂比值的影响,并探讨其在子痫前期中可能的作用机制。方法选取2015年6月至2017年10月于本院产科住院的子痫前期患者(子痫前期组)203例、正常妊娠孕妇(正常妊娠组)210例及健康未孕育龄期女性(健康非孕组)200例。采集母体静脉血和新生儿脐血,分别测定葡萄糖、甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)、载脂蛋白A1、载脂蛋白B100和脂蛋白a的水平,并计算TG/HDL-C、TC/HDL-C、LDL-C/HDL-C、log(TG/HDL-C)及动脉粥样硬化指数(atherosclerosis index,AI)。采用聚合酶链反应-限制性片段长度多态性(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)技术检测脂蛋白代谢相关基因LPL S447X、N291S位点的多态性,评估基因多态性对健康非孕组、正常妊娠组和子痫前期组患者血脂及血脂比值的影响。结果与健康非孕组和正常妊娠组比较,子痫前期组母体LPL S447X的X等位基因基因型频率降低,差异有显著性(P<0.05),母体LPL基因N291S位点基因多态性在3组间差异无显著性(P>0.05)。根据母体LPL基因S447X多态性位点分组,正常妊娠组的SX/XX基因型母体TG/HDL-C及log(TG/HDL-C)均显著低于SS基因型(P<0.05);子痫前期组中LPL基因S447X SX/XX基因型的母体TG、TC、TC/HDL-C、TG/HDL-C、LDL-C/HDL-C及AI均显著低于SS基因型(P<0.05)。新生儿脐血的血脂及血脂比值在母体LPL基因S447X SX/XX基因型和SS基因型间差异均无显著性(P>0.05)。以母体LPL基因N291S多态性位点分组,正常妊娠组及子痫前期组母体和新生儿血脂及血脂比值组间差异均无显著性(P>0.05)。结论脂蛋白代谢相关基因LPL的S447X突变携带者患子痫前期的风险显著降低;而LPL基因N291S多态性位点多态性可能与子痫前期发病无关。母体脂蛋白代谢相关基因多态性对母体和新生儿血脂均有一定影响,但单个基因多态性对血脂的影响有限,当对血脂有影响作用的环境改变时,如发生子痫前期时才会产生较为显著的影响。

Objective In this study, we examined the associations between the polymorphisms of lipoprotein metabolism related genes LPL S447X, N291S loci and pre-eclampsia, which might influence the maternal and fetal blood lipid profile and ratios, and then to explore the possible pathological mechanisms. Method Subjects,including 200 healthy non-pregnant women, 210 uncomplicated pregnant women and 203 pregnant women complicated by pre-eclampsia, were selected from the Department of Obstetric in our hospital. Serums from maternal and newborn were analyzed for lipid profiles, and the ratios of lipid were calculated. PCR-RFLP were used to detect the polymorphisms of lipoprotein metabolism related genes LPL S447X, N291S gene loci, assessed the effects of genetic polymorphism on blood lipid and lipid ratios in healthy non-pregnant, uncomplicated pregnant and pre-eclampsia groups. Result Comparing to healthy non-pregnant women and uncomplicated pregnant women, maternal LPL gene S447X locus genotype frequency in pre-eclampsia has significant difference（P〈0.05）. Maternal LPL N291S locus gene polymorphism had no significant difference among the three groups. These results showed that maternal LPL gene S447X mutation carriers could significantly reduce the risk of pre-eclampsia, while the maternal LPL gene N291S polymorphism might not be associated with the pathogenesis of pre-eclampsia.Cases grouped according to maternal LPL gene S447X loci polymorphism, maternal blood lipid ratio TG/HDL-C and log（TG/HDL-C） of SX/XX genotype in uncomplicated pregnant women were significantly lower than that of SS genotype（P〈0.05）, and maternal blood lipid TG, TC,TC/HDL-C, TG/HDL-C, LDL-C/HDL-C and AI of SX/XX genotype in pre-eclampsia group were significantly lower than that of SS genotype（P〈0.05）. The polymorphisms of maternal LPL gene N291S were grouped, and there was no significant difference between uncomplicated pregnant group and pre-eclampsia group in blood lipid and blood lipid ratio between mother and newborn（P〉0.05）. Conclusion Lipoprotein metabolism related genes LPL gene S447X mutation carriers can significantly reduce the risk of pre-eclampsia. LPL gene N291S locus gene polymorphisms may not be associated with the pathogenesis of pre-eclampsia.The results of this study indicate that maternal lipoprotein metabolism related genes polymorphisms on maternal and fetal lipid changes have certain effect, but a single gene polymorphism has a limited effects on lipidprofiles, and when the affecting environmental changed, such as pre-eclampsia, the cumulative effect is more obvious.