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

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

doi:10.1016/j.ajhg.2018.08.002

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

Am J Hum Genet. 2018 Sep 6;103(3):367-376. doi: 10.1016/j.ajhg.2018.08.002. Epub 2018 Aug 30.

Authors

Kimberly J Reidy¹, Rebecca C Hjorten², Claire L Simpson³, Avi Z Rosenberg⁴, Stacy D Rosenblum⁵, Csaba P Kovesdy⁶, Frances A Tylavsky⁷, Joseph Myrie¹, Bianca L Ruiz¹, Soulin Haque¹, Khyobeni Mozhui⁸, George W Nelson⁹, Victor A David¹⁰, Xiaoping Yang⁴, Masako Suzuki¹¹, Jack Jacob¹², Sandra E Reznik¹³, Frederick J Kaskel¹, Jeffrey B Kopp¹⁴, Cheryl A Winkler¹⁵, Robert L Davis¹⁶

Affiliations

¹ Department of Pediatrics, Division of Pediatric Nephrology, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
² Department of Pediatrics, Division of Pediatric Nephrology, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Pediatrics, Division of Nephrology and Hypertension, Cincinnati Children's Hospital, Cincinnati OH 45229, USA.
³ Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
⁴ Department of Pathology, John's Hopkins University, Baltimore, MD 21218, USA.
⁵ Department of Pediatrics, Division of Neonatology, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
⁶ Department of Medicine, Division of Nephrology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
⁷ Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
⁸ 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.
⁹ 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.
¹⁰ Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
¹¹ Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
¹² Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
¹³ Departments of Pathology and Obstetrics & Gynecology and Women's Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Pharmaceutical Sciences, St. John's University, Queens, NY 11439, USA.
¹⁴ Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, MD 20814, USA.
¹⁵ 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.
¹⁶ Center for Biomedical Informatics, Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38103, USA. Electronic address: rdavis88@uthsc.edu.

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.

Keywords: APOL1; African American; fetal genotype; health disparity; preeclampsia; prematurity.

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Apolipoprotein L1 / genetics*
Biomarkers / blood*
Biomarkers / metabolism
Black or African American / genetics*
Case-Control Studies
Female
Fetus / metabolism*
Genetic Testing / methods
Genotype
Humans
Mothers
Pre-Eclampsia / blood
Pre-Eclampsia / genetics*
Pre-Eclampsia / metabolism
Pregnancy
Risk

Substances

APOL1 protein, human
Apolipoprotein L1
Biomarkers

Abstract

Publication types

MeSH terms

Substances

Grants and funding