Yu Ni1, Claire L Simpson2, Robert L Davis3, Adam A Szpiro4, Catherine J Karr5, Csaba P Kovesdy6, Rebecca C Hjorten7, Frances A Tylavsky8, Nicole R Bush9, Kaja Z LeWinn10, Cheryl A Winkler11, Jeffrey B Kopp12, Yoshitsugu Obi13. 1. Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA, USA. Electronic address: niyu@uw.edu. 2. Department of Genetics, Genomics and Informatics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA. 3. Center for Biomedical Informatics, University of Tennessee Health Science Center, Memphis, TN, USA; Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA. 4. Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA. 5. Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA, USA; Department of Pediatrics, School of Medicine, University of Washington, Seattle, WA, USA; Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA. 6. Division of Nephrology, University of Tennessee Health Science Center, Memphis, TN, USA; Nephrology Section, Memphis VA Medical Center, Memphis, TN, USA. 7. Pediatrics Division of Nephrology, Seattle Children's Hospital, Seattle, WA, USA. 8. Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN, USA. 9. Department of Psychiatry and Behavioral Sciences, School of Medicine, University of California, San Francisco, San Francisco, CA, USA; Department of Pediatrics, School of Medicine, University of California, San Francisco, San Francisco, CA, USA. 10. Department of Psychiatry and Behavioral Sciences, School of Medicine, University of California, San Francisco, San Francisco, CA, USA. 11. Basic Research Laboratory, Molecular Genetic Epidemiology Section, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD, USA. 12. Kidney Disease Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. 13. Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA; Department of Medicine-Nephrology, University of Tennessee Health Science Center, Memphis, TN, USA.
Abstract
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 μ 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-μg/m3 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; Pinteraction = 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 (Pinteraction = 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.
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 μ 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-μg/m3 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; Pinteraction = 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 (Pinteraction = 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.
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