TY - JOUR
T1 - APOL1 kidney risk variants and cardiovascular disease
T2 - An individual participant data meta-analysis
AU - Grams, Morgan E.
AU - Surapaneni, Aditya
AU - Ballew, Shoshana H.
AU - Appel, Lawrence J.
AU - Boerwinkle, Eric
AU - Boulware, L. Ebony
AU - Chen, Teresa K.
AU - Coresh, Josef
AU - Cushman, Mary
AU - Divers, Jasmin
AU - Gutiérrez, Orlando M.
AU - Irvin, Marguerite R.
AU - Ix, Joachim H.
AU - Kopp, Jeffrey B.
AU - Kuller, Lewis H.
AU - Langefeld, Carl D.
AU - Lipkowitz, Michael S.
AU - Mukamal, Kenneth J.
AU - Musani, Solomon K.
AU - Naik, Rakhi P.
AU - Pajewski, Nicholas M.
AU - Peralta, Carmen A.
AU - Tin, Adrienne
AU - Wassel, Christina L.
AU - Wilson, James G.
AU - Winkler, Cheryl A.
AU - Young, Bessie A.
AU - Zakai, Neil A.
AU - Freedman, Barry I.
N1 - Publisher Copyright:
© 2019 by the American Society of Nephrology.
PY - 2019
Y1 - 2019
N2 - Background Two coding variants in the apo L1 gene (APOL1) are strongly associated with kidney disease in blacks. Kidney disease itself increases the risk of cardiovascular disease, butwhether these variants have an independent direct effect on the risk of cardiovascular disease is unclear. Previous studies have had inconsistent results. MethodsWe conducted a two-stage individual participant data meta-analysis to assess the association of APOL1 kidney-risk variants with adjudicated cardiovascular disease events and death, independent of kidney measures. The analysis included 21,305 blacks from eight large cohorts. Results Over 8.9±5.0 years of follow-up, 2076 incident cardiovascular disease events occurred in the 16,216 participants who did not have cardiovascular disease at study enrollment. In fully-adjusted analyses, individuals possessing two APOL1 kidney-risk variants had similar risk of incident cardiovascular disease (coronary heart disease, myocardial infarction, stroke and heart failure; hazard ratio 1.11, 95% confidence interval, 0.96 to 1.28) compared to individuals with zero or one kidney-risk variant. The risk of coronary heart disease, myocardial infarction, stroke and heart failure considered individually was also comparable by APOL1 genotype. APOL1 genotype was also not associated with death. There was no difference in adjusted associations by level of kidney function, age, diabetes status, or body-mass index. Conclusions In this large, two-stage individual participant data meta-analysis, APOL1 kidney-risk variants were not associated with incident cardiovascular disease or death independent of kidney measures.
AB - Background Two coding variants in the apo L1 gene (APOL1) are strongly associated with kidney disease in blacks. Kidney disease itself increases the risk of cardiovascular disease, butwhether these variants have an independent direct effect on the risk of cardiovascular disease is unclear. Previous studies have had inconsistent results. MethodsWe conducted a two-stage individual participant data meta-analysis to assess the association of APOL1 kidney-risk variants with adjudicated cardiovascular disease events and death, independent of kidney measures. The analysis included 21,305 blacks from eight large cohorts. Results Over 8.9±5.0 years of follow-up, 2076 incident cardiovascular disease events occurred in the 16,216 participants who did not have cardiovascular disease at study enrollment. In fully-adjusted analyses, individuals possessing two APOL1 kidney-risk variants had similar risk of incident cardiovascular disease (coronary heart disease, myocardial infarction, stroke and heart failure; hazard ratio 1.11, 95% confidence interval, 0.96 to 1.28) compared to individuals with zero or one kidney-risk variant. The risk of coronary heart disease, myocardial infarction, stroke and heart failure considered individually was also comparable by APOL1 genotype. APOL1 genotype was also not associated with death. There was no difference in adjusted associations by level of kidney function, age, diabetes status, or body-mass index. Conclusions In this large, two-stage individual participant data meta-analysis, APOL1 kidney-risk variants were not associated with incident cardiovascular disease or death independent of kidney measures.
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U2 - 10.1681/ASN.2019030240
DO - 10.1681/ASN.2019030240
M3 - Article
C2 - 31383730
AN - SCOPUS:85071662643
SN - 1046-6673
VL - 30
SP - 2027
EP - 2036
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 10
ER -