P 40 Infant but not maternal APOL1 variant genotypes are associated with increased risk for preeclampsia in African Americans

Abstract

Introduction APOL1 genetic variants are common among African Americans (AA), and account for much of the increased risk of chronic kidney disease among AA. APOL1 is abundantly transcribed in the placenta, shows abnormal expression in preeclampsia and APOL1 transgenic mice manifest preeclampsia. As AAs are at elevated risk for preeclampsia, prematurity and low birth weight, we studied the relationship between these conditions and APOL1 status. Methods CANDLE (Conditions Affecting Neurocognitive Development and Learning in Early Childhood), is a study of 1503 mothers and infants, including 990 AA women. Gestational age was determined by ultrasound or reported last menstrual cycle. Birthweight and pregnancy complications were abstracted from mother’s medical record. APOL1 genotyping was performed with TaqMan assay and validated by Sanger sequencing. Mothers and children were categorized as having 0, 1 or 2 risk alleles (RA) (with 2 RA denoting risk variant homozygotes or compound heterozygotes). Multivariate analyses for a recessive model were performed, adjusted for maternal age, income, and gender. Population attributable risk was calculated using standard approaches. Results Among 990 AA CANDLE mothers, the mean delivery age was 24.7 y and mean gestational age was 38.7 w. Of 921 genotyped mothers, 100 (10.9%) had 2 risk alleles (RA); of 747 genotyped children, 103 (13.8%) had 2 RAs. There was no association between maternal or child APOL1 status and gestational age or birth weight among all pregnancies or when the analysis excluded mothers with electively induced labor or C-sections. An increased risk for preeclampsia was seen with the child’s APOL1 2 RA status. Among all pregnancies, mothers of children with 2 RA status had a 1.9-fold increase in risk for preeclampsia (OR 1.9; 95% CI 1.1,3.5). When electively induced labor and C-sections were excluded, the risk for preeclampsia among mothers of children with 2 RA was further increased (OR 2.1; 95% CI 1.1,4.0). Discussion Mothers of children with APOL1 2RA status are at an increased risk for preeclampsia. Our results suggest that approximately 10% of preeclampsia among AA is related to APOL1.