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Decreased ALCAM expression and promoter hypermethylation is associated with preeclampsia

Hypertension Research volume 43, pages 13–22 (2020)Cite this article

Abstract

Preeclampsia (PE) is a major obstetrical complication that results in maternal and fetal morbidity and mortality. Aberrant epigenetic modifications are widely involved in the pathogenesis of PE. Previously, the activated leukocyte cell adhesion molecule (ALCAM) was reported to be required for blastocyst implantation but has not been described in the context of pathological pregnancy. This study explored the expression of ALCAM and its methylation levels in the placentas and peripheral venous blood of patients with PE from a Chinese Han population. The mRNA and protein expression levels of ALCAM were downregulated in the PE placentas compared with the control placentas (P < 0.05). The methylation rate of the ALCAM gene promoter was considerably elevated in the placentas (P = 0.003, odds ratio (OR) = 0.264, 95% confidence interval (95% CI) [0.108–0.647], cases n = 47, controls n = 53) and peripheral blood (P = 0.007, OR = 0.455, 95% CI [0.256–0.806], cases n = 100, controls n = 100) of the PE patients compared with those of the normotensive women, suggesting a negative relationship between ALCAM methylation and gene transcription. Moreover, the transcriptional expression of ALCAM was dramatically increased by demethylating treatment in trophoblastic cells. ALCAM is expected to be involved in the pathogenesis of PE through methylation regulation.

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Funding

This research was supported by funding from the National Science Foundation of the P.R. China (No. 81600211); the Science Foundation of Shandong Province (ZR2016HM28 and ZR2014HP017); and by the Application and Basic Research Project of Qingdao (18-2-2-27-jch).

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Author notes

  1. These authors contributed equally: Li-li Wei, Yue-shuai Pan

  2. These authors contributed equally: Lu Zhang, Shi-guo Liu

Authors and Affiliations

  1. Department of Nursing, The Affiliated Hospital of Qingdao University, Qingdao, China

    Li-li Wei, Yue-shuai Pan & Yu-fang Gao

  2. Prenatal Diagnosis Center, The Affiliated Hospital of Qingdao University, Qingdao, China

    Qian Tang, Lu Zhang & Shi-guo Liu

  3. Department of Clinical Laboratory, Qingdao Women and Children’s Hospital, Qingdao, China

    Zong-jun Yang

  4. Department of Clinical Laboratory, Qingdao Municipal Hospital, Qingdao, China

    Wei-qing Song

  5. Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, China

    Jing Li

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  1. Li-li Wei
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Contributions

Conceptualization, LZ and SL; Data curation, LZ and SL; Formal analysis, JL; Funding acquisition, LZ and SL; Investigation, ZY and WS; Methodology, QT and LZ; Project administration, LZ and SL; Resources, SL; Software, LW and YP; Supervision, ZY, WS, YG, QT and JL; Validation, LW, YP and YG; Writing—original draft, LW and YP; Writing—review and editing, LZ and SL.

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Correspondence to Lu Zhang or Shi-guo Liu.

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Wei, Ll., Pan, Ys., Tang, Q. et al. Decreased ALCAM expression and promoter hypermethylation is associated with preeclampsia. Hypertens Res 43, 13–22 (2020). https://doi.org/10.1038/s41440-019-0337-0

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