Date of Award

11-2022

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Program

Biomedical Sciences

Track

Cell Biology and Physiology

Research Advisor

Claire L. Simpson, PhD

Committee

Joyce L. Browne, MD; Athena S. Davenport, PhD; Robert L. Davis, MD; Kyhobeni Mozhui, PhD

Keywords

APOL1, Genetics, Micronutrients, Preeclampsia

Abstract

Preeclampsia (PE) is a hypertensive disorder of pregnancy that is associated with micronutrient deficiencies. Nutrients involved in placental health and maintenance, such as vitamin D and folate, are important nutrients to assess in the risk of PE. As gestational age increases, the levels of vitamin D and folate potentially have incrementally increasing concentrations associated with PE. In addition to micronutrient deficiencies, PE is also associated with the presence of APOL1 high-risk (HR) variants. It was also hypothesized that a potential additive effect exists between HR APOL1 genotype status and nutritional deficiencies that would place individuals at a higher risk of developing PE. A systematic and meta-analysis was conducted to assess the hypothesis that vitamin D and folate levels were risk factors for PE based on specific gestational time periods. Additionally, a case-control study was conducted using a subset of African American mother and infant dyads collected from the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) cohort in Memphis, TN. This study included maternal blood samples that assessed serum vitamin D and folate levels during the 2nd and 3rd trimesters of pregnancy. Logistic regression model was used to further assess whether maternal or fetal apolipoprotein genotype status modified the association with PE and folate or vitamin D. In addition to maternal blood samples, reported micronutrient intake of calcium, magnesium, selenium and folate were also assessed. Low vitamin D and folate levels were associated with the development of PE in the systematic review and meta-analyses. Case-control studies further evaluated this association and expanded current understanding by assessing vitamin D and folate deficiencies in conjunction with APOL1 genotype status. When having a child with HR APOL1 genotype, African American women with 25(OH)D lower than 20 ng/mL in the 2nd or 3rd trimester were found to have a two-fold and six-fold increased odds of developing PE. We found a similar association with the assessment of folate levels. Individuals with plasma folate less than 15 ng/mL within the 2nd trimester and a child with fetal APOL1 HR genotype were at a three-fold risk of developing PE. Findings suggest the importance of nutrigenetics in future PE research.

Declaration of Authorship

Declaration of Authorship is included in the supplemental files.

ORCID

https://orcid.org/0000-0002-9028-331X

DOI

10.21007/etd.cghs.2022.0608

Additional Files
2022-026-Bruner-DOA.pdf (129 kB)
Declaration of Authorship
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