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Copy Number Analyses Identified a Novel Gene: APOBEC3A Related to Lipid Metabolism in the Pathogenesis of Preeclampsia

文献类型：期刊论文

作者Liu, Nan5,6; Guo, Yu-Na4; Wang, Xiao-Jin3; Ma, Jue4; He, Yun-Ting3; Zhang, Fang2; He, Hao3; Xie, Jin-Liang3; Zhuang, Xu1; Liu, Meng5,6
刊名FRONTIERS IN CARDIOVASCULAR MEDICINE
出版日期2022-05-16
卷号9页码:13
关键词preeclampsia APOBEC3A lipid metabolism copy number variation genetics
ISSN号2297-055X
DOI10.3389/fcvm.2022.841249
通讯作者Gong, Li-Kun(lkgong@cdser.simm.ac.cn) ; Wang, Bing-Shun(wangbingshun@sjtu.edu.cn)
英文摘要BackgroundPreeclampsia is a heterogeneous and complex disease with its pathogenesis mechanism not fully elucidated. A certain subset of patients with preeclampsia exhibit disturbances in lipid metabolism before clinical symptoms. Moreover, there is a tendency for preeclampsia to run in families. Whether genetic factors play a role in abnormal lipid metabolism during the incidence of preeclampsia has not been well investigated. MethodsPreeclampsia patients (n = 110) and healthy age- and gravidity-matched pregnant women (n = 110) were enrolled in this study. Peripheral blood specimens were used for genomic analysis (n = 10/group) or laboratory validation (n = 100/group). We retrospectively obtained the baseline clinical characteristics of 68 preeclampsia patients and 107 controls in early pregnancy (12-14 gestational weeks). Correlation analyses between differential genes and baseline lipid profiles were performed to identify candidate genes. In vitro and in vivo gain-of-function models were constructed with lentivirus and adeno-associated virus systems, respectively, to investigate the role of candidate genes in regulating lipid metabolism and the development of preeclampsia. ResultsWe observed that preeclampsia patients exhibited significantly elevated plasma TC (P = 0.037) and TG (P < 0.001) levels and increased body mass index (P = 0.006) before the disease onset. Within the region of 27 differential copy number variations, six genes potentially connected with lipid metabolism were identified. The aberrant copies of APOBEC3A, APOBEC3A_B, BTNL3, and LMF1 between preeclampsia patients and controls were verified by quantitative polymerase chain reaction. Especially, APOBEC3A showed a significant positive correlation with TC (P < 0.001) and LDL (P = 0.048) in early pregnancy. Then, our in vitro data revealed that overexpression of APOBEC3A disrupted lipid metabolism in HepG2 cells and affected both cholesterol and fatty acid metabolisms. Finally, in vivo study in a hepatic-specific overexpressed APOBEC3A mouse model revealed abnormal parameters related to lipid metabolism. Pregnant mice of the same model at the end of pregnancy showed changes related to preeclampsia-like symptoms, such as increases in sFlt-1 levels and sFlt-1/PLGF ratios in the placenta and decreases in fetal weight. ConclusionOur findings established a new link between genetics and lipid metabolism in the pathogenesis of preeclampsia and could contribute to a better understanding of the molecular mechanisms of preeclampsia.
WOS关键词LIPOPROTEIN ; PREGNANCY ; WOMEN ; HYPERTENSION ; IMPACT
资助项目National Natural Science Foundation of China[81573162]
WOS研究方向Cardiovascular System & Cardiology
语种英语
WOS记录号WOS:000804212100001
出版者FRONTIERS MEDIA SA
源URL[http://119.78.100.183/handle/2S10ELR8/301163]  
专题新药研究国家重点实验室
通讯作者Gong, Li-Kun; Wang, Bing-Shun
作者单位1.Shanghai Jiao Tong Univ, Renji Hosp, Dept Obstet & Gynecol, Sch Med, Shanghai, Peoples R China
2.Shanghai Jiao Tong Univ, Renji Hosp, Sch Renji Clin Med, Sch Med, Shanghai, Peoples R China
3.Shanghai Jiao Tong Univ, Clin Res Inst, Dept Biostat, Sch Med, Shanghai, Peoples R China
4.Shanghai Jiao Tong Univ, Int Peace Matern & Child Hlth Hosp, Dept Obstet, Sch Med, Shanghai, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Safety Evaluat & Res, State Key Lab Drug Res, Shanghai, Peoples R China
6.Univ Chinese Acad Sci, Sch Pharm, Beijing, Peoples R China
推荐引用方式
GB/T 7714		 Liu, Nan,Guo, Yu-Na,Wang, Xiao-Jin,et al. Copy Number Analyses Identified a Novel Gene: APOBEC3A Related to Lipid Metabolism in the Pathogenesis of Preeclampsia[J]. FRONTIERS IN CARDIOVASCULAR MEDICINE,2022,9:13.
APA Liu, Nan.,Guo, Yu-Na.,Wang, Xiao-Jin.,Ma, Jue.,He, Yun-Ting.,...&Wang, Bing-Shun.(2022).Copy Number Analyses Identified a Novel Gene: APOBEC3A Related to Lipid Metabolism in the Pathogenesis of Preeclampsia.FRONTIERS IN CARDIOVASCULAR MEDICINE,9,13.
MLA Liu, Nan,et al."Copy Number Analyses Identified a Novel Gene: APOBEC3A Related to Lipid Metabolism in the Pathogenesis of Preeclampsia".FRONTIERS IN CARDIOVASCULAR MEDICINE 9(2022):13.

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来源：上海药物研究所

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