APOL1 Nephropathy Risk Alleles and Mortality in African American Adults: A Cohort Study

Orlando M. Gutiérrez, Marguerite R. Irvin, Neil A. Zakai, Rakhi Prakash Naik, Ninad S. Chaudhary, Michelle M. Estrella, Sophie Limou, Suzanne E. Judd, Mary Cushman, Jeffrey B. Kopp, Cheryl A. Winkler

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalAmerican Journal of Kidney Diseases
DOIs
StateAccepted/In press - Jan 1 2019

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African Americans
Cohort Studies
Alleles
Mortality
Genotype
Chronic Renal Insufficiency
Kidney
Albuminuria
Genetic Models
Proportional Hazards Models

Keywords

  • African American
  • APOL1 genotype
  • Apolipoprotein L1 (APOL1)
  • chronic kidney disease (CKD)
  • CKD progression
  • genetic differences
  • genetic risk factor
  • mortality
  • nephropathy
  • racial/ethnic disparities
  • risk allele
  • survival

ASJC Scopus subject areas

  • Nephrology

Cite this

Gutiérrez, O. M., Irvin, M. R., Zakai, N. A., Naik, R. P., Chaudhary, N. S., Estrella, M. M., ... Winkler, C. A. (Accepted/In press). APOL1 Nephropathy Risk Alleles and Mortality in African American Adults: A Cohort Study. American Journal of Kidney Diseases. https://doi.org/10.1053/j.ajkd.2019.05.027

APOL1 Nephropathy Risk Alleles and Mortality in African American Adults : A Cohort Study. / Gutiérrez, Orlando M.; Irvin, Marguerite R.; Zakai, Neil A.; Naik, Rakhi Prakash; Chaudhary, Ninad S.; Estrella, Michelle M.; Limou, Sophie; Judd, Suzanne E.; Cushman, Mary; Kopp, Jeffrey B.; Winkler, Cheryl A.

In: American Journal of Kidney Diseases, 01.01.2019.

Research output: Contribution to journalArticle

Gutiérrez, OM, Irvin, MR, Zakai, NA, Naik, RP, Chaudhary, NS, Estrella, MM, Limou, S, Judd, SE, Cushman, M, Kopp, JB & Winkler, CA 2019, 'APOL1 Nephropathy Risk Alleles and Mortality in African American Adults: A Cohort Study', American Journal of Kidney Diseases. https://doi.org/10.1053/j.ajkd.2019.05.027
Gutiérrez, Orlando M. ; Irvin, Marguerite R. ; Zakai, Neil A. ; Naik, Rakhi Prakash ; Chaudhary, Ninad S. ; Estrella, Michelle M. ; Limou, Sophie ; Judd, Suzanne E. ; Cushman, Mary ; Kopp, Jeffrey B. ; Winkler, Cheryl A. / APOL1 Nephropathy Risk Alleles and Mortality in African American Adults : A Cohort Study. In: American Journal of Kidney Diseases. 2019.
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abstract = "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.",
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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 Prakash

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.

PY - 2019/1/1

Y1 - 2019/1/1

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 - African American

KW - APOL1 genotype

KW - Apolipoprotein L1 (APOL1)

KW - chronic kidney disease (CKD)

KW - CKD progression

KW - genetic differences

KW - genetic risk factor

KW - mortality

KW - nephropathy

KW - racial/ethnic disparities

KW - risk allele

KW - survival

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