单基因高血压相关基因变异与子痫前期关联性研究

Association of monogenic hypertension related genetic variations with preeclampsia

目的探讨单基因高血压相关基因变异与子痫前期(preeclampsia,PE)的相关性。方法收集2016年9月至2018年9月收住福建省立医院妇产科的92例PE患者(PE组)和35例正常妊娠产妇(对照组)的外周血,检测41个单基因高血压相关基因的罕见变异谱;通过SIFT、PolyPhen、MutationTaster和CADD等多重评分软件评价其致病性。结果在127例入选者中检测出32种基因变异,其中PE组的CACNA1D基因变异频率(9.8%)明显高于千人基因组计划(2.4%)或中国千人高血压项目(2.7%)非妊娠高血压女性(P<0.05),c.920A>G和c.4475G>A为新的变异位点,多重评分软件提示均可能具有致病性,发生CACNA1D变异的9个PE患者均出现不良临床结局。结论CACNA1D变异可能与子痫前期相关。

Objective To investigate the relationship between genetic variations related to monogenic hypertension and preeclampsia(PE).Methods Peripheral blood samples of 92 PE patients(PE group)and 35 normal pregnant women(control group)admitted to our hospital were collected from September 2016 to September 2018.The rare variation profile of 41 monogenic hypertension related genes were screened.Pathogenicity was evaluated by multi-score software including SIFT,Polyphen,Mutationtaster and CADD.Results A total of 32 genetic variants were detected in 127 enrollees.The frequency of CACNA1D gene mutation in PE group(9.8%)was significantly higher than that in the 1000 Genome Project(2.4%)or nonpregnant hypertensive females in Hypertension Program-1000 in China(2.7%)(P<0.05).c.920A>G and c.4475G>A were novel mutations.The result of multi-score software suggested that all the mutations may be pathogenic,and nine PE patients with CACNA1D mutation had adverse clinical outcomes.Conclusion The CACNA1D gene mutation may be associated with preeclampsia.