Apolipoprotein L1 gene variants associate with prevalent kidney but not prevalent cardiovascular disease in the Systolic Blood Pressure Intervention Trial

Langefeld, Carl D.; Divers, Jasmin; Pajewski, Nicholas M.; Hawfield, Amret; Reboussin, David M.; Bild, Diane E.; Kaysen, George A.; Kimmel, Paul L.; Raj, Dominic S.; Ricardo, Ana C.; Wright, Jackson T.; Sedor, John R.; Rocco, Michael V.; Freedman, Barry I.

doi:10.1038/ki.2014.254

Cited by 77 publications

(107 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We found no association between the APOL1 risk variants and incident MI, coronary heart disease, or stroke. These findings are in accordance with results from the ARIC (Atherosclerosis Risk in Communities) study and SPRINT trial, which also reported no significant association between the APOL1 high‐risk variants and incident or prevalent CVD, respectively 20, 25. On the other hand, the JHS and WHI (Women's Health Initiative) both demonstrated a significantly increased risk for a major adverse cardiovascular event among people with 2 versus 0 APOL1 high‐risk alleles,21 whereas the CHS noted an increased risk of MI but not stroke or cardiovascular mortality 22.…”

Section: Discussionsupporting

confidence: 91%

“…On the other hand, the JHS and WHI (Women's Health Initiative) both demonstrated a significantly increased risk for a major adverse cardiovascular event among people with 2 versus 0 APOL1 high‐risk alleles,21 whereas the CHS noted an increased risk of MI but not stroke or cardiovascular mortality 22. The reasons for these discrepant findings are unclear, although differences in study populations likely contribute, including varying ages and comorbidities 20, 21, 22, 25…”

Section: Discussionmentioning

confidence: 99%

“…Studies to date on this topic, however, have been conflicting. In a cross‐sectional analysis of SPRINT (Systolic Blood Pressure Intervention Trial), an increasing number of APOL1 risk variants was not associated with prevalent clinical atherosclerotic CVD 20. In longitudinal analyses of community‐based blacks, postmenopausal women, or older individuals, APOL1 risk variants have been associated with increased cardiovascular morbidity 21, 22.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Association Between APOL1 Genotypes and Risk of Cardiovascular Disease in MESA (Multi‐Ethnic Study of Atherosclerosis)

Chen

Katz

Estrella

et al. 2017

JAHA

View full text Add to dashboard Cite

Background APOL1 genetic variants confer an increased risk for kidney disease. Their associations with cardiovascular disease (CVD) are less certain. We aimed to compare the prevalence of subclinical CVD and incidence of atherosclerotic CVD and heart failure by APOL1 genotypes among self‐identified black participants of MESA (Multi‐Ethnic Study of Atherosclerosis).Methods and ResultsCross‐sectional associations of APOL1 genotypes (high‐risk=2 alleles; low‐risk=0 or 1 allele) with coronary artery calcification, carotid‐intimal media thickness, and left ventricular mass were evaluated using logistic and linear regression. Longitudinal associations of APOL1 genotypes with incident myocardial infarction, stroke, coronary heart disease, and congestive heart failure were examined using Cox regression. We adjusted for African ancestry, age, and sex. We also evaluated whether hypertension or kidney function markers explained the observed associations. Among 1746 participants with APOL1 genotyping (mean age 62 years, 55% women, mean cystatin C–based estimated glomerular filtration rate 89 mL/min per 1.73 m2, 12% with albuminuria), 12% had the high‐risk genotypes. We found no difference in prevalence or severity of coronary artery calcification, carotid‐intimal media thickness, or left ventricular mass by APOL1 genotypes. The APOL1 high‐risk group was 82% more likely to develop incident heart failure compared with the low‐risk group (95% confidence interval, 1.01–3.28). Adjusting for hypertension (hazard ratio, 1.80; 95% confidence interval, 1.00–3.24) but not markers of kidney function (hazard ratio, 1.86; 95% confidence interval, 1.03–3.35) slightly attenuated this association. The APOL1 high‐risk genotypes were not significantly associated with other clinical CVD outcomes.ConclusionsAmong blacks without baseline CVD, the APOL1 high‐risk variants may be associated with increased risk for incident heart failure but not subclinical CVD or incident clinical atherosclerotic CVD.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Association Between APOL1 Genotypes and Risk of Cardiovascular Disease in MESA (Multi‐Ethnic Study of Atherosclerosis)

Chen

Katz

Estrella

et al. 2017

JAHA

View full text Add to dashboard Cite

show abstract

“…Ito et al reported association of two APOL1 risk alleles (odds ratio approximately 2) with atherosclerotic events in the Jackson Heart Study, with replication in the Women's Health Initiative study, 26 although this was not replicated in the large Systolic Blood Pressure Intervention Trial. 27 Numerous genomewide association studies and admixture linkage mapping studies have not identified chromosome 22 as a locus for systolic blood pressure or hypertension, suggesting that APOL1 variants probably do not contribute to primary hypertension.…”

Section: The Similarity Of Thementioning

confidence: 99%

APOL1 Risk Alleles Are Associated with Exaggerated Age-Related Changes in Glomerular Number and Volume in African-American Adults

Hoy

Hughson

Kopp

et al. 2015

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

APOL1 genetic variants contribute to kidney disease in African Americans. We assessed correlations between APOL1 profiles and renal histological features in subjects without renal disease. Glomerular number (N glom ) and mean glomerular volume (V glom ) were measured by the dissector/fractionator method in kidneys of African-American and non-African-American adults without renal disease, undergoing autopsies in Jackson, Mississippi. APOL1 risk alleles were genotyped and the kidney findings were evaluated in the context of those profiles. The proportions of African Americans with none, one, and two APOL1 risk alleles were 38%, 43%, and 19%, respectively; 38% of African Americans had G1 allele variants and 31% of African Americans had G2 allele variants. Only APOL1-positive African Americans had significant reductions in N glom and increases in V glom with increasing age. Regression analysis predicted an annual average loss of 8834 (P=0.03, sex adjusted) glomeruli per single kidney over the first 38 years of adult life in African Americans with two risk alleles. Body mass index above the group medians, but below the obesity definition of $30 kg/m 2 , enhanced the expression of age-related changes in N glom in African Americans with either one or two APOL1 risk alleles. These findings indicate that APOL1 risk alleles are associated with exaggerated age-related nephron loss, probably decaying from a larger pool of smaller glomeruli in early adult life, along with enlargement of the remaining glomeruli. These phenomena might mark mechanisms of accentuated susceptibility to kidney disease in APOL1-positive African Americans.

show abstract

“…Similarly, the recognition of much higher incidence and prevalence and mortality from kidney disease among blacks as compared to whites, especially at younger ages, originally attributed in most epidemiological studies to the higher prevalence of hypertension and diabetes among blacks, was in part due to striking differences in the frequency of ApoL, a gene related to susceptibility to trypanosomiasis that is much higher in the black as compared to white population [85,86]. Similarly, studies of Greenlandic Inuit have led to interesting interrelationships of diet and genetic polymorphisms and possible diseases [87].…”

Section: The Independent Variables Are Not Accurate or Repeatablementioning

confidence: 99%

The limitations of opportunistic epidemiology, pseudopod epidemiology

Kuller

2016

Eur J Epidemiol

View full text Add to dashboard Cite

Epidemiology has been remarkably successful in the past in identifying the important agents of disease, the impact of the environment, both physical and social, and interrelationship with host susceptibility (genomics). Many of the advances in improving the health of individuals and populations have been the result of epidemiology studies that have identified the specific ''agents'' of disease and application of public health and preventive medicine. In recent years, large longitudinal studies have dominated epidemiology research, especially long incubation period chronic diseases. The initial hypotheses in these studies have been expanded by vertical extension studies using newer technologies to measure independent variables, vertical pseudopods, and additional studies of other diseases, horizontal pseudopods, of the original longitudinal study. Host susceptibility, i.e. genomics, has also become a prominent component of these longitudinal studies. The critical question addressed in this paper is whether these ''pseudopod'' epidemiology approaches have enhanced public health or generated a large number of studies of little impact.

show abstract

Apolipoprotein L1 gene variants associate with prevalent kidney but not prevalent cardiovascular disease in the Systolic Blood Pressure Intervention Trial

Cited by 77 publications

References 29 publications

Association Between APOL1 Genotypes and Risk of Cardiovascular Disease in MESA (Multi‐Ethnic Study of Atherosclerosis)

Association Between APOL1 Genotypes and Risk of Cardiovascular Disease in MESA (Multi‐Ethnic Study of Atherosclerosis)

APOL1 Risk Alleles Are Associated with Exaggerated Age-Related Changes in Glomerular Number and Volume in African-American Adults

The limitations of opportunistic epidemiology, pseudopod epidemiology

Contact Info

Product

Resources

About