TY - JOUR
T1 - Association of apol1 genotypes with measures of microvascular and endothelial function, and blood pressure in mesa
AU - Chen, Teresa K.
AU - Katz, Ronit
AU - Estrella, Michelle M.
AU - Post, Wendy S.
AU - Kramer, Holly
AU - Rotter, Jerome I.
AU - Tayo, Bamidele
AU - Mychaleckyj, Josyf C.
AU - Wassel, Christina L.
AU - Peralta, Carmen A.
N1 - Funding Information:
Chen was supported by the Extramural Grant Program by Satellite Healthcare, a not-for-profit renal care provider and Clinician Scientist Career Development Award from Johns Hopkins University and is currently supported by a George M. O’Brien Center for Kidney Research Pilot and Feasibility Grant from Yale University (under Award Number NIH/NIDDKP30DK079310) and K08DK117068 from NIH/NIDDK. MESA and the MESA SHARe project are conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) and the National Center for Advancing Translational Sciences (NCATS) in collaboration with MESA investigators. Support for MESA is provided by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169 from NHLBI, UL1-TR-000040, UL1-TR-001079, UL1-TR-001420, UL1-TR-001881 from NCATS, and DK063491 from NIH/NIDDK. Funding for SHARe genotyping was provided by NHLBI contract N02-HL-64278. Genotyping was performed at Affymetrix (Santa Clara, California) and the Broad Institute of Harvard and MIT (Boston, Massachusetts) using the Affymetrix Genome-Wide Human SNP Array 6.0.
Funding Information:
Chen was supported by the Extramural Grant Program by Satellite Healthcare, a not-for-profit renal care provider and Clinician Scientist Career Development Award from Johns Hopkins University and is currently supported by a George M. O’Brien Center for Kidney Research Pilot and Feasibility Grant from Yale University (under Award Number NIH/NIDDK P30DK079310) and K08DK117068 from NIH/NIDDK. MESA and the MESA SHARe project are conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) and the National Center for Advancing Translational Sciences (NCATS) in collaboration with MESA investigators. Support for MESA is provided by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169 from NHLBI, UL1-TR-000040, UL1-TR-001079, UL1-TR-001420, UL1-TR-001881 from NCATS, and DK063491 from NIH/NIDDK. Funding for SHARe geno-typing was provided by NHLBI contract N02-HL-64278. Genotyping was performed at Affymetrix (Santa Clara, California) and the Broad Institute of Harvard and MIT (Boston, Massachusetts) using the Affymetrix Genome-Wide Human SNP Array 6.0.
Publisher Copyright:
© 2020 The Authors.
PY - 2020
Y1 - 2020
N2 - BACKGROUND: APOL1 high-risk genotypes are associated with increased risk for hypertension-attributed kidney disease among Black adults in the United States. Biopsy studies show differences in kidney vasculature by APOL1 status; less is known about the variants’ associations with systemic vascular and endothelial function. Whether APOL1 risk variants are associated with blood pressure (BP) is also uncertain. METHODS AND RESULTS: Using linear regression, we examined cross-sectional associations of APOL1 risk genotypes (high=2 risk alleles, low=0 or 1 risk allele) with subclinical measures of vascular function (small arterial elasticity, n=1586; large arterial elasticity, n=1586; ascending aortic distensibility, n=985) and endothelial function (flow-mediated dilation, n=777). Using linear mixed-effects models, we studied longitudinal associations of APOL1 risk genotypes with BP (n=1619), adjusting for age, sex, and African ancestry. Among 1619 (12% APOL1 high-risk) Black participants in MESA (Multi-Ethnic Study of Atherosclerosis), mean age was 62 years old, 58% had hypertension, and mean systolic BP was 131 mm Hg at baseline. At examination 1 (2000–2002), there was no significant difference in small arterial elasticity, large arterial elasticity, ascending aortic distensibility, or flow-mediated dilation in participants with APOL1 high-versus low-risk genotypes (P>0.05 for all). Over a mean follow-up of 7.8 years, relative annual changes in systolic and diastolic BP and pulse pressure did not differ significantly by APOL1 risk status (between-group differences of −0.20, −0.14, and −0.25, respectively; P>0.05 for all). CONCLUSIONS: Among Black participants in MESA, APOL1 high-risk genotypes were not associated with subclinical vascular and endothelial function or BP trajectories. The relationship of APOL1 with kidney disease may be intrinsic to the kidney rather than through peripheral effects on systemic vasculature or BP.
AB - BACKGROUND: APOL1 high-risk genotypes are associated with increased risk for hypertension-attributed kidney disease among Black adults in the United States. Biopsy studies show differences in kidney vasculature by APOL1 status; less is known about the variants’ associations with systemic vascular and endothelial function. Whether APOL1 risk variants are associated with blood pressure (BP) is also uncertain. METHODS AND RESULTS: Using linear regression, we examined cross-sectional associations of APOL1 risk genotypes (high=2 risk alleles, low=0 or 1 risk allele) with subclinical measures of vascular function (small arterial elasticity, n=1586; large arterial elasticity, n=1586; ascending aortic distensibility, n=985) and endothelial function (flow-mediated dilation, n=777). Using linear mixed-effects models, we studied longitudinal associations of APOL1 risk genotypes with BP (n=1619), adjusting for age, sex, and African ancestry. Among 1619 (12% APOL1 high-risk) Black participants in MESA (Multi-Ethnic Study of Atherosclerosis), mean age was 62 years old, 58% had hypertension, and mean systolic BP was 131 mm Hg at baseline. At examination 1 (2000–2002), there was no significant difference in small arterial elasticity, large arterial elasticity, ascending aortic distensibility, or flow-mediated dilation in participants with APOL1 high-versus low-risk genotypes (P>0.05 for all). Over a mean follow-up of 7.8 years, relative annual changes in systolic and diastolic BP and pulse pressure did not differ significantly by APOL1 risk status (between-group differences of −0.20, −0.14, and −0.25, respectively; P>0.05 for all). CONCLUSIONS: Among Black participants in MESA, APOL1 high-risk genotypes were not associated with subclinical vascular and endothelial function or BP trajectories. The relationship of APOL1 with kidney disease may be intrinsic to the kidney rather than through peripheral effects on systemic vasculature or BP.
KW - APOL1
KW - Apolipoprotein L1
KW - Arterial stiffness
KW - Blood pressure
KW - Hypertension
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U2 - 10.1161/JAHA.120.017039
DO - 10.1161/JAHA.120.017039
M3 - Article
C2 - 32851884
AN - SCOPUS:85090171891
SN - 2047-9980
VL - 9
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 17
M1 - e017039
ER -