Associations between APOL1 genetic variants and blood pressure in African American mothers and children from a US pregnancy cohort: Modification by air pollution exposures

Introduction: Carriage of high-risk APOL1 genetic variants is associated with increased risks for kidney diseases in people of African descent. Less is known about the variants' associations with blood pressure or potential moderators. Methods: We investigated these associations in a pregnancy cohort of 556 women and 493 children identified as African American. Participants with two APOL1 risk alleles were defined as having the high-risk genotype. Blood pressure in both populations was measured at the child's 4-6 years visit. We fit multivariate linear and Poisson regressions and further adjusted for population stratification to estimate the APOL1-blood pressure associations. We also examined the associations modified by air pollution exposures (particulate matter <= 2.5 mu m in aerodynamic diameter [PM2.5] and nitrogen dioxide) and explored other moderators such as health conditions and behaviors. Results: Neither APOL1 risk alleles nor risk genotypes had a main effect on blood pressure in mothers or children. However, each 2-mu g/m(3) increase of four-year average PM2.5 was associated with a 16.3 (95%CI: 5.7, 26.9) mmHg higher diastolic blood pressure in mothers with the APOL1 high-risk genotype, while the estimated effect was much smaller in mothers with the low-risk genotype (i.e., 2.9 [95%CI: -3.1, 8.8] mmHg; P-interaction = 0.01). Additionally, the associations of APOL1 risk alleles and the high-risk genotype with high blood pressure (i.e., SBP and/or DBP >= 90th percentile) were stronger in girls vs. boys (P-interaction = 0.02 and 0.005, respectively). Conclusion: This study sheds light on the distribution of high blood pressure by APOL1 genetic variants and informs regulatory policy to protect vulnerable population subgroups.