Joint Associations of Maternal-Fetal APOL1 Genotypes and Maternal Country of Origin With Preeclampsia Risk.

RATIONALE & OBJECTIVE Preeclampsia, disproportionately affecting 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 Blacks, 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 on the APOL1- preeclampsia association. STUDY DESIGN Nested case-control study. SETTING & PARTICIPANTS 426 Black mother-infant pairs (275 African-Americans; 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 effect 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 (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 blomerular 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.