@article{733331371c9e4631b17911233cd4e1ae,
title = "Joint Associations of Maternal-Fetal APOL1 Genotypes and Maternal Country of Origin With Preeclampsia Risk",
abstract = "Rationale & Objectives: Preeclampsia, which disproportionately affects Black women, is a leading cause of preterm delivery and risk for future hypertension and chronic kidney disease (CKD). Apolipoprotein L1 (APOL1) kidney risk alleles, common among Black individuals, contribute substantially to CKD disparities. Given the strong link between preeclampsia and CKD, we investigated whether maternal and fetal APOL1 risk alleles can jointly influence preeclampsia risk, and explored potential modifiers of the association between APOL1 and preeclampsia. Study Design: Nested case-control study. Setting & Participants: 426 Black mother-infant pairs (275 African Americans and 151 Haitians) from the Boston Birth Cohort. Exposure: Maternal and fetal APOL1 risk alleles. Outcomes: Preeclampsia. Analytical Approach: Logistic regression models with adjustment for demographic characteristics were applied to analyze associations between fetal and maternal APOL1 risk alleles and risk of preeclampsia and to investigate the effects of modification by maternal country of origin. Results: Fetal APOL1 risk alleles tended to be associated with an increased risk of preeclampsia, which was not statistically significant in the total genotyped population. However, this association was modified by maternal country of origin (P < 0.05 for interaction tests): fetal APOL1 risk alleles were significantly associated with an increased risk of preeclampsia among African Americans under recessive (odds ratio [OR], 3.6 [95% CI, 1.3-9.7]; P = 0.01) and additive (OR, 1.7 [95% CI, 1.1-2.6]; P = 0.01) genetic models but not in Haitian Americans. Also, maternal-fetal genotype discordance at the APOL1 locus was associated with a 2.6-fold higher risk of preeclampsia (P < 0.001) in African Americans. Limitations: Limited sample size in stratified analyses; self-reported maternal country of origin; pre-pregnancy estimated glomerular filtration rate (eGFR) and proteinuria data in mothers were not collected; unmeasured confounding social and/or environmental factors; no replication study. Conclusions: This study supports the hypothesis that fetal APOL1 kidney risk alleles are associated with increased risk for preeclampsia in a recessive mode of inheritance in African Americans and suggests that maternal-fetal genotype discordance is also associated with this risk. These conclusions underscore the need to better understand maternal-fetal interaction and their genetic and environmental factors as contributors to ethnic disparities in preeclampsia.",
keywords = "APOL1, African Americans, Haitian, US-born, ancestry, apolipoprotein L1 gene, country of origin, ethnic disparities, fetal genetics, kidney risk allele, maternal-fetal genotype discordance, non–US-born, preeclampsia, pregnancy complication, risk allele",
author = "Xiumei Hong and Rosenberg, {Avi Z.} and Boyang Zhang and Elizabeth Binns-Roemer and Victor David and Yiming Lv and Hjorten, {Rebecca C.} and Reidy, {Kimberly J.} and Chen, {Teresa K.} and Guoying Wang and Yuelong Ji and Simpson, {Claire L.} and Davis, {Robert L.} and Kopp, {Jeffrey B.} and Xiaobin Wang and Winkler, {Cheryl A.}",
note = "Funding Information: Xiumei Hong, MD, PhD, Avi Z. Rosenberg, MD, PhD, Boyang Zhang, BS, Elizabeth Binns-Roemer, BS, Victor David, MS, Yiming Lv, BS, Rebecca C. Hjorten, MD, Kimberly J. Reidy, MD, Teresa K. Chen, MD, MHS, Guoying Wang, MD, PhD, Yuelong Ji, PhD, Claire L. Simpson, PhD, Robert L. Davis, MD, MPH, Jeffrey B. Kopp, MD, Xiaobin Wang, MD, MPH, ScD, and Cheryl A. Winkler, PhD. Contributed to the study design: AZR, XH, XW, CAW, JBK; oversaw the genotyping performed in this study and genetic analyses: CAW, VD; performed data cleaning and data analyses: XH, BZ, YL; provided critical inputs on study design, data analyses, interpretation of the study findings: all authors; founded and principal investigator of the Boston Birth Cohort (the parent study): XW; oversaw participant recruitment and data collection for the parent study: XW; contributed to participant recruitment and data collection for the parent study: XH, GW, YJ. Each author contributed important intellectual content during manuscript drafting or revision and agrees to be personally accountable for the individual's own contributions and to ensure that questions pertaining to the accuracy or integrity of any portion of the work, even one in which the author was not directly involved, are appropriately investigated and resolved, including with documentation in the literature if appropriate. The Boston Birth Cohort (the parent study) was supported by National Insitutes of Health (NIH) grants R03HD096136, R21HD085556, 2R01HD041702, R01HD086013, R01HD098232, and R21AI154233. This project was supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Intramural Research Program grant ZO1 DK-043308 (to JBK), an NIH Bench to Bedside grant supplementing ZO1 DK-043308 and 3R01HD098232-02S1, and National Cancer Institute of NIH Intramural Research Program (to Dr Winkler) and under contract HHSN26120080001E. Dr Hong is supported by the Johns Hopkins Population Center (Eunice Kennedy Shriver National Institute of Child Health and Human Development grant R24HD042854). Dr Chen was supported by the Extramural Grant Program by Satellite Healthcare, a not-for-profit renal care provider. Dr Reidy receives support from a catalytic seed grant (NIH Clinical and Translational Science Award 1 UL1 TR001073 [Einstein/Montefiore]), NIDDK, and the Preeclampsia Foundation. The funders were not involved in study design, data collection, analysis, reporting, or the decision to submit for publication. The authors declare that they have no relevant financial interests. The authors thank study participants in the Boston Birth Cohort study for their support. The authors also thank for the dedication and hard work of the field team at the Department of Pediatrics, Boston University School of Medicine, and for the support of the obstetric nursing staff at Boston Medical Center. The authors also thank Linda Rosen, Boston University Clinical Data Warehouse, for assistance in obtaining relevant clinical information. The Clinical Data Warehouse service is supported by Boston University Clinical and Translational Institute and the NIH Clinical and Translational Science Award U54-TR001012. Research reported in this publication was supported through the NIH Bench-to-Bedside award made possible by Office of Research on Women's Health (ORWH). The content of this publication does not necessarily reflect the view or policy of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the government. Received April 23, 2020. Evaluated by 2 external peer reviewers, with direct editorial input from a Statistics/Methods Editor, an Associate Editor, and the Editor-in-Chief. Accepted in revised form October 24, 2020. Funding Information: The authors thank study participants in the Boston Birth Cohort study for their support. The authors also thank for the dedication and hard work of the field team at the Department of Pediatrics, Boston University School of Medicine, and for the support of the obstetric nursing staff at Boston Medical Center. The authors also thank Linda Rosen, Boston University Clinical Data Warehouse, for assistance in obtaining relevant clinical information. The Clinical Data Warehouse service is supported by Boston University Clinical and Translational Institute and the NIH Clinical and Translational Science Award U54-TR001012. Funding Information: Research reported in this publication was supported through the NIH Bench-to-Bedside award made possible by Office of Research on Women{\textquoteright}s Health (ORWH). The content of this publication does not necessarily reflect the view or policy of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the government. Funding Information: The Boston Birth Cohort (the parent study) was supported by National Insitutes of Health ( NIH) grants R03HD096136 , R21HD085556 , 2R01HD041702 , R01HD086013 , R01HD098232 , and R21AI154233 . This project was supported by National Institute of Diabetes and Digestive and Kidney Diseases ( NIDDK) Intramural Research Program grant ZO1 DK-043308 (to JBK), an NIH Bench to Bedside grant supplementing ZO1 DK-043308 and 3R01HD098232-02S1 , and National Cancer Institute of NIH Intramural Research Program (to Dr Winkler) and under contract HHSN26120080001E. Dr Hong is supported by the Johns Hopkins Population Center (Eunice Kennedy Shriver National Institute of Child Health and Human Development grant R24HD042854) . Dr Chen was supported by the Extramural Grant Program by Satellite Healthcare, a not-for-profit renal care provider. Dr Reidy receives support from a catalytic seed grant (NIH Clinical and Translational Science Award 1 UL1 TR001073 [Einstein/Montefiore]), NIDDK, and the Preeclampsia Foundation. The funders were not involved in study design, data collection, analysis, reporting, or the decision to submit for publication. Publisher Copyright: {\textcopyright} 2020 National Kidney Foundation, Inc.",
year = "2021",
month = jun,
doi = "10.1053/j.ajkd.2020.10.020",
language = "English (US)",
volume = "77",
pages = "879--888.e1",
journal = "American Journal of Kidney Diseases",
issn = "0272-6386",
publisher = "W.B. Saunders Ltd",
number = "6",
}