Apolipoprotein L1 variants and risk of preeclampsia and preterm birth in African American women

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PROJECT SUMMARY/ABSTRACT The proposed study will be the first large prospective study from a general population of African American (AA) women to address a critical unknown—whether the moderately common mutations only observed among individuals of recent African ancestry, apolipoprotein L-1 (APOL1) variants, are associated with increased risk of preeclampsia and/or preterm birth among AA women, a population that disproportionally suffers from both conditions. Despite the well-known excess burden and deaths in AA women from preeclampsia and preterm birth, our current understanding of genetic predisposition to preeclampsia and preterm birth is rudimentary. Common coding variants in the apolipoprotein L-1 gene have been shown to be very strong risk factors for a spectrum of kidney disease in AAs. These risk variants on chromosome 22 are highly prevalent in people from Sub-Saharan Africa, an area with the highest rate of preeclampsia and preterm birth worldwide. Several studies in basic science support a potential role of APOL1 in the etiology of preeclampsia and the pathophysiology of preterm birth. However, results of human studies on APOL1 genotype with risk of preeclampsia and preterm birth are conflicting and have relied on relatively small samples with conflicting results. Epidemiological evidence from a generalized population of AA women with sufficient statistical power is urgently needed to fill the knowledge gap of whether APOL1 genotype predisposes AA women to a higher risk of preeclampsia and preterm birth. We propose to test these hypotheses in a large prospective cohort of AA women from across the United States, the Black Women's Health Study (BWHS). The BWHS has 25 years of longitudinal data, with repeatedly collected information on pregnancy, birth outcomes, lifestyle factors, and medical history, in addition to biospecimen samples collected from 29,601 women. APOL1 genotype data are already available for 9,355 BWHS participants. We propose to additionally genotype 1,052 samples from women with preeclampsia and will use a 2:1 matched case-control study design to test our hypothesis. Findings from this study will add new insights on the complex pathophysiology of preeclampsia and preterm birth among AAs, and help to identify early risk indicators for pregnancy complications. The huge disparity in maternal morbidity and mortality experienced by AA women must be addressed. The proposed study has the potential to provide information that can be used to inform earlier detection and possible prevention of certain pregnancy complications.