Maternal APOL1 Genotypes and Preeclampsia Risk

Background: APOL1 risk alleles are prevalent in individuals of West African ancestry and associated with increased risk of kidney disease. Although preeclampsia disproportionately affects women of Black ethnic backgrounds, evidence linking APOL1 alleles to preeclampsia remains conflicting. Objectives: The purpose of this study was to explore whether maternal APOL1 alleles contribute to preeclampsia risk and associated adverse pregnancy outcomes. Study design: We conducted a nested case-control study of 5210 pregnant women, including 745 preeclampsia cases and 949 controls of Black self-reported ethnicity, 1385 preeclampsia cases and 2131 controls of White self-reported ethnicity. APOL1 G1 and G2 risk alleles were directly genotyped on the Illumina Infinium Global Screening Array. Associations with preeclampsia, early preeclampsia, recurrent preeclampsia, birthweight centiles and gestational age at delivery were examined using regression models assuming a recessive mode of inheritance with adjustment for established risk factors and stratification by self-reported ethnicity and genetically-determined ancestry. Results: Presence of APOL1 risk alleles was almost exclusively observed in women of Black self-reported ethnicity. 168/949 controls (17.7%) and 133/745 cases (17.9%) carried two APOL1 risk alleles, and these women did not have a significantly increased risk of preeclampsia compared to those with zero or one APOL1 risk alleles in adjusted analyses (OR 1.00, 95% CI 0.76-1.29, p=0.972). When restricting analysis to women of Black self-reported ethnicity only, no association was observed between APOL1 genotype and preeclampsia risk (adjusted OR 0.94, 95% CI 0.61-1.25, p=0.673). When restricting analysis to women of pan-African genetically-determined ancestry only, also no association was observed between APOL1 genotype and preeclampsia risk (adjusted OR 1.00, 95% CI 0.76-1.32). No associations were found between number of APOL1 risk alleles and early preeclampsia, recurrent preeclampsia, birthweight centile or gestational age at delivery after adjustment for established risk factors and stratification by self-reported ethnicity or genetically-determined ancestry. Conclusions: Maternal APOL1 risk alleles do not independently influence preeclampsia risk or related adverse outcomes in a multi-ethnic pregnancy study. Future studies should examine whether fetal APOL1 genotypes, alone or in interaction with maternal genotypes, contribute to preeclampsia risk.