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Fetal-not Maternal-APOL1 Genotype Associated with Risk for Preeclampsia in Those with African Ancestry

  1. Author:
    Reidy, Kimberly J
    Hjorten, Rebecca C
    Simpson, Claire L
    Rosenberg, Avi Z
    Rosenblum, Stacy D
    Kovesdy, Csaba P
    Tylavsky, Frances A
    Myrie, Joseph
    Ruiz, Bianca L
    Haque, Soulin
    Mozhui, Khyobeni
    Nelson, George
    David, Victor
    Yang, Xiaoping
    Suzuki, Masako
    Jacob, Jack
    Reznik, Sandra E
    Kaskel, Frederick J
    Kopp, Jeffrey B
    Winkler, Cheryl
    Davis, Robert L

  2. Author Address

    Department of Pediatrics, Division of Pediatric Nephrology, Children 39;s Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Department of Pediatrics, Division of Pediatric Nephrology, Children 39;s Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Pediatrics, Division of Nephrology and Hypertension, Cincinnati Children 39;s Hospital, Cincinnati OH 45229, USA., Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN 38163, USA., Department of Pathology, John 39;s Hopkins University, Baltimore, MD 21218, USA., Department of Pediatrics, Division of Neonatology, Children 39;s Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Department of Medicine, Division of Nephrology, University of Tennessee Health Science Center, Memphis, TN 38163, USA., Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA., Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN 38163, USA; Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA., Advanced Biomedical Computational Science, Biomedical Informatics & Data Science Program, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, MD 21701, USA., Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA., Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Departments of Pathology and Obstetrics & Gynecology and Women 39;s Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Pharmaceutical Sciences, St. John 39;s University, Queens, NY 11439, USA., Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, MD 20814, USA., Basic Research Laboratory, Molecular Genetic Epidemiology Section, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, MD 21702, USA. Electronic address: winklerc@mail.nih.gov., Center for Biomedical Informatics, Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38103, USA. Electronic address: rdavis88@uthsc.edu.,
    1. Year: 2018
    2. Date: Sep 6
    3. Epub Date: 2018 08 21
  2. Journal: American journal of human genetics
    1. 103
    2. 3
    3. Pages: 367-376
  4. Type of Article: Article
  5. ISSN: 0002-9297
  1. Abstract:

    Black Americans are at increased risk for preeclampsia. Genetic variants in apolipoprotein L1 (APOL1) account for much of the increased risk for kidney disease in blacks. APOL1 is expressed in human placenta and transgenic mice expressing APOL1 develop preeclampsia. We evaluated the role of APOL1 variants in human preeclampsia. We determined maternal and fetal APOL1 genotypes in black women with preeclampsia in two populations. At Einstein Montefiore Center (EMC) Affiliated Hospitals, we studied 121 pregnancies in black women with preeclampsia. At University of Tennessee Health Science Center (UTHSC), we studied 93 pregnancies in black women with preeclampsia and 793 pregnancies without preeclampsia. We measured serum markers of preeclampsia soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF), and soluble endoglin (sEng). Fetal APOL1 high-risk (HR) genotype was associated with preeclampsia, with odds ratios at EMC and UTHSC of 1.84 (95% CI 1.11, 2.93) and 1.92 (95% CI 1.05, 3.49), respectively. Maternal APOL1 HR genotype was not associated with preeclampsia. Mothers with the fetal APOL1 HR genotype had more cerebral or visual disturbances (63% versus 37%, p = 0.04). In addition, fetal APOL1 HR genotype was associated with a higher sFLT-1/PlGF ratio at birth (p = 0.04). Fetal APOL1 high-risk genotype increases the risk for preeclampsia, likely by adversely affecting placental function. Further research is needed to assess whether APOL1 genetic testing can predict preeclampsia and improve pregnancy outcomes. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.ajhg.2018.08.002
  3. PMID: 30173819
  4. PMCID: PMC6128247
  5. View record in Web of Science®
  6. WOS: 000443819500006
  7. PII : S0002-9297(18)30268-4

Library Notes

  1. Fiscal Year: FY2017-2018
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