TY - JOUR
T1 - APOL1 Nephropathy Risk Alleles and Mortality in African American Adults
T2 - A Cohort Study
AU - Gutiérrez, Orlando M.
AU - Irvin, Marguerite R.
AU - Zakai, Neil A.
AU - Naik, Rakhi P.
AU - Chaudhary, Ninad S.
AU - Estrella, Michelle M.
AU - Limou, Sophie
AU - Judd, Suzanne E.
AU - Cushman, Mary
AU - Kopp, Jeffrey B.
AU - Winkler, Cheryl A.
N1 - Funding Information:
Orlando M. Guti?rrez, MD, MMSc, Marguerite R. Irvin, PhD, Neil A. Zakai, MD, Rakhi P. Naik, MD, MHS, Ninad S. Chaudhary, MBBS, MPH, Michelle M. Estrella, MD, MHS, Sophie Limou, PhD, Suzanne E. Judd, PhD, Mary Cushman, MD, MSc, Jeffrey B. Kopp, MD, and Cheryl A. Winkler, PhD. Conceived and designed study: OMG, MRI, JBK, CAW; involved in data acquisition: RPN, SEJ, NAZ, MC, CAW; analyzed data: OMG, NC; involved in data interpretation: OMG, MRI, NAZ, RPN, MME, SL, SEJ, MC, JBK, CAW. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. This study was supported by cooperative agreement U01 NS041588 from the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute on Aging (NIA), National Institutes of Health (NIH), Department of Health and Human Services. Dr Guti?rrez was supported by R01NS080850, U01DK102730, and K24DK116180 from the NIH, and a Strategically Focused Research Network in Disparities in Cardiovascular Disease grant from the American Heart Association (15SFDRN25620022). Dr Kopp was supported by the Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, MD. Dr Winkler was funded in part with federal funds from the National Cancer Institute (NCI), NIH, under contract HHSN26120080001E and supported in part by the Intramural Research Program of the NIH, NCI, Center for Cancer Research. Representatives from the funding sources did not have a role in study design, data collection, analysis, reporting or the decision to submit for publication. The authors declare that they have no relevant financial interests. The authors thank the other investigators, the staff, and the participants in the REGARDS Study for valuable contributions. A full list of participating REGARDS investigators and institutions can be found at www.regardsstudy.org. The content of this publication does not necessarily reflect the views or policies of the NINDS, NIA, NIDDK, NCI, NIH, or the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. Received January 14, 2019. Evaluated by 2 external peer reviewers, with direct editorial input from a Statistics/Methods Editor and an Associate Editor, who served as Acting Editor-in-Chief. Accepted in revised form May 22, 2019. The involvement of an Acting Editor-in-Chief was to comply with AJKD's procedures for potential conflicts of interest for editors, described in the Information for Authors & Journal Policies.
Funding Information:
This study was supported by cooperative agreement U01 NS041588 from the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute on Aging (NIA), National Institutes of Health (NIH), Department of Health and Human Services . Dr Gutiérrez was supported by R01NS080850 , U01DK102730 , and K24DK116180 from the NIH , and a Strategically Focused Research Network in Disparities in Cardiovascular Disease grant from the American Heart Association ( 15SFDRN25620022 ). Dr Kopp was supported by the Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, MD. Dr Winkler was funded in part with federal funds from the National Cancer Institute (NCI), NIH , under contract HHSN26120080001E and supported in part by the Intramural Research Program of the NIH , NCI , Center for Cancer Research. Representatives from the funding sources did not have a role in study design, data collection, analysis, reporting or the decision to submit for publication.
Publisher Copyright:
© 2019
PY - 2020/1
Y1 - 2020/1
N2 - Rationale & Objective: APOL1 nephropathy risk alleles are associated with the development of chronic kidney disease (CKD) in African Americans. Although CKD is an established risk factor for mortality, associations of APOL1 risk alleles with mortality are uncertain. Study Design: Prospective cohort. Settings & Participants: 10,380 African American and 17,485 white American participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study. Exposures: APOL1 nephropathy risk alleles. Outcomes: All-cause and cause-specific mortality. Analytical Approach: Cox proportional hazards models were used to examine the association of APOL1 high-risk genotypes (2 risk alleles) versus APOL1 low-risk genotypes (0/1 risk allele) with all-cause and cause-specific mortality in African Americans and examine the risk for all-cause mortality in African Americans with high-risk genotypes versus African Americans with low-risk genotypes and white Americans. Results: APOL1 high-risk participants were younger and had a higher prevalence of albuminuria than low-risk participants. There was no statistically significant association of APOL1 high- versus low-risk genotypes with all-cause mortality in models adjusted for sociodemographic variables, comorbid conditions, and kidney function (HR, 0.88; 95% CI, 0.77-1.01). After further adjustment for genetic ancestry in a subset with available data, a statistically significant association emerged (HR, 0.81; 95% CI, 0.69-0.96). Associations differed by CKD status (Pinteraction = 0.04), with African Americans with high-risk genotypes having lower risk for mortality than those with low-risk genotypes in fully adjusted models (HR, 0.78; 95% CI, 0.62-0.99) among those with CKD, but not those without CKD (HR, 0.84; 95% CI, 0.66-1.05). Compared with white Americans, African Americans with high-risk genotypes had a similar rate of mortality, whereas African Americans with low-risk genotypes had a higher rate of mortality (HR, 1.07; 95% CI, 1.00-1.14) in fully adjusted models. Limitations: Lack of follow-up measures of kidney function. Conclusions: African Americans with high-risk APOL1 genotypes had lower mortality than those with low-risk genotypes in multivariable-adjusted models including genetic ancestry.
AB - Rationale & Objective: APOL1 nephropathy risk alleles are associated with the development of chronic kidney disease (CKD) in African Americans. Although CKD is an established risk factor for mortality, associations of APOL1 risk alleles with mortality are uncertain. Study Design: Prospective cohort. Settings & Participants: 10,380 African American and 17,485 white American participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study. Exposures: APOL1 nephropathy risk alleles. Outcomes: All-cause and cause-specific mortality. Analytical Approach: Cox proportional hazards models were used to examine the association of APOL1 high-risk genotypes (2 risk alleles) versus APOL1 low-risk genotypes (0/1 risk allele) with all-cause and cause-specific mortality in African Americans and examine the risk for all-cause mortality in African Americans with high-risk genotypes versus African Americans with low-risk genotypes and white Americans. Results: APOL1 high-risk participants were younger and had a higher prevalence of albuminuria than low-risk participants. There was no statistically significant association of APOL1 high- versus low-risk genotypes with all-cause mortality in models adjusted for sociodemographic variables, comorbid conditions, and kidney function (HR, 0.88; 95% CI, 0.77-1.01). After further adjustment for genetic ancestry in a subset with available data, a statistically significant association emerged (HR, 0.81; 95% CI, 0.69-0.96). Associations differed by CKD status (Pinteraction = 0.04), with African Americans with high-risk genotypes having lower risk for mortality than those with low-risk genotypes in fully adjusted models (HR, 0.78; 95% CI, 0.62-0.99) among those with CKD, but not those without CKD (HR, 0.84; 95% CI, 0.66-1.05). Compared with white Americans, African Americans with high-risk genotypes had a similar rate of mortality, whereas African Americans with low-risk genotypes had a higher rate of mortality (HR, 1.07; 95% CI, 1.00-1.14) in fully adjusted models. Limitations: Lack of follow-up measures of kidney function. Conclusions: African Americans with high-risk APOL1 genotypes had lower mortality than those with low-risk genotypes in multivariable-adjusted models including genetic ancestry.
KW - APOL1 genotype
KW - African American
KW - Apolipoprotein L1 (APOL1)
KW - CKD progression
KW - chronic kidney disease (CKD)
KW - genetic differences
KW - genetic risk factor
KW - mortality
KW - nephropathy
KW - racial/ethnic disparities
KW - risk allele
KW - survival
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U2 - 10.1053/j.ajkd.2019.05.027
DO - 10.1053/j.ajkd.2019.05.027
M3 - Article
C2 - 31563468
AN - SCOPUS:85072563353
VL - 75
SP - 54
EP - 60
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
SN - 0272-6386
IS - 1
ER -