Association of <i>APOL1</i> With Heart Failure With Preserved Ejection Fraction in Postmenopausal African American Women

Franceschini, Nora; Kopp, Jeffrey B.; Barac, Ana; Martin, Lisa W.; Li, Yun; Qian, Huijun; Reiner, Alex P.; Pollak, Martin R.; Wallace, Robert B.; Rosamond, Wayne D.; Winkler, Cheryl A.

doi:10.1001/jamacardio.2018.1827

Cited by 15 publications

(13 citation statements)

References 47 publications

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“…It is possible that blood pressure differences do exist between those with and without APOL1 risk alleles with more severe hypertension, or in those with overt kidney disease. Similar to other studies [32], a significant difference was found in baseline kidney function measured by serum creatinine and eGFR in those with two APOL1 risk alleles, without significant differences detected in baseline albuminuria. Although much research has focused on the podocyte as a site of APOL1-induced injury, a difference in eGFR occurring without albuminuria suggests the mechanism of renal disease may not limited to the glomerulus or may affect the glomerulus in patterns beyond classic focal segmental glomerulosclerosis [33].…”

Section: Discussionsupporting

confidence: 88%

Hypertensive APOL1 risk allele carriers demonstrate greater blood pressure reduction with angiotensin receptor blockade compared to low risk carriers

et al. 2019

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BackgroundHypertension (HTN) disproportionately affects African Americans (AAs), who respond better to thiazide diuretics than other antihypertensives. Variants of the APOL1 gene found in AAs are associated with a higher rate of kidney disease and play a complex role in cardiovascular disease.MethodsAA subjects from four HTN trials (n = 961) (GERA1, GERA2, PEAR1, and PEAR2) were evaluated for blood pressure (BP) response based on APOL1 genotype after 4–9 weeks of monotherapy with thiazides, beta blockers, or candesartan. APOL1 G1 and G2 variants were determined by direct sequencing or imputation.ResultsBaseline systolic BP (SBP) and diastolic BP (DBP) levels did not differ based on APOL1 genotype. Subjects with 1–2 APOL1 risk alleles had a greater SBP response to candesartan (-12.2 +/- 1.2 vs -7.5 +/- 1.8 mmHg, p = 0.03; GERA2), and a greater decline in albuminuria with candesartan (-8.3 +/- 3.1 vs +3.7 +/- 4.3 mg/day, p = 0.02). APOL1 genotype did not associate with BP response to thiazides or beta blockers. GWAS was performed to determine associations with BP response to candesartan depending on APOL1 genotype. While no SNPs reached genome wide significance, SNP rs10113352, intronic in CSMD1, predicted greater office SBP response to candesartan (p = 3.7 x 10−7) in those with 1–2 risk alleles, while SNP rs286856, intronic in DPP6, predicted greater office SBP response (p = 3.2 x 10−7) in those with 0 risk alleles.ConclusionsHypertensive AAs without overt kidney disease who carry 1 or more APOL1 risk variants have a greater BP and albuminuria reduction in response to candesartan therapy. BP response to thiazides or beta blockers did not differ by APOL1 genotype. Future studies confirming this initial finding in an independent cohort are required.

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Section: Discussionsupporting

confidence: 88%

Hypertensive APOL1 risk allele carriers demonstrate greater blood pressure reduction with angiotensin receptor blockade compared to low risk carriers

et al. 2019

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“…We noted that the APOL1 high‐risk genotypes were not associated with an increased risk for all‐cause mortality. This is in line with findings from the African American Study of Kidney Disease and Hypertension (AASK; mean age = 54 years), the Women's Health Initiative (mean age = 62 years), and the Systolic Blood Pressure Intervention Trial (mean age about 64 years), all of which reported a lack of association between APOL1 and all‐cause mortality 23‐25 . In contrast, the CHS (mean age about 74 years) reported a borderline increased risk for total mortality associated with the APOL1 high‐risk genotypes (adjusted HR = 1.3; 95% CI = 1.0–1.7; P = .05), 14 whereas the African American Diabetes Heart Study (mean age about 56 years) reported a survival advantage associated with the APOL1 risk variants 26 .…”

Section: Discussionsupporting

confidence: 80%

Race, APOL1 Risk Variants, and Clinical Outcomes among Older Adults: The ARIC Study

Chen

Coresh

Ballew

et al. 2020

J American Geriatrics Society

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BACKGROUND/OBJECTIVES: APOL1 high-risk genotypes confer an increased risk for kidney disease, but their clinical significance among older adults remains unclear. We aimed to determine whether APOL1 genotype status (high risk = 2 risk alleles; low risk = 0-1 risk alleles) and selfreported race (Black; White) are associated with number of hospitalizations, incident chronic kidney disease (CKD), endstage renal disease (ESRD), and mortality among older adults participating in a community-based cohort study. DESIGN: Observational longitudinal cohort study. SETTING: The Atherosclerosis Risk in Communities (ARIC) study. PARTICIPANTS: Community-dwelling older adults (mean age = 75.8 years; range = 66-90 years). RESULTS: Among 5,564 ARIC participants (78.2% White, 19.1% APOL1 low-risk Black, and 2.7% APOL1 high-risk Black), the proportion with creatinine and cystatin C-based estimated glomerular filtration rate (eGFR CrCys ) below 60 mL/min/1.73 m 2 at baseline was 40.6%, 34.8%, and 43.2%, respectively. Over a mean follow-up of 5.1 years, APOL1 high-risk Blacks had a 2.67-fold higher risk for ESRD compared with low-risk Blacks (95% confidence interval [CI] = 1.05-6.79) in models adjusted for age and sex. This association was no longer significant upon further adjustment for baseline eGFR CrCys and albuminuria (hazard ratio [HR] = 1.08; 95% CI = .39-2.96). Rate of hospitalizations and risks of mortality and incident CKD did not differ significantly by APOL1 genotype status. Compared with Whites, Blacks had 1.85-fold and 3.45-fold higher risks for incident CKD and ESRD, respectively, in models adjusted for age, sex, eGFR CrCys , and albuminuria. These associations persisted after additional adjustments for clinical/socioeconomic factors and APOL1 genotype (incident CKD: HR = 1.38; 95% CI = 1.06-1.81; ESRD: HR = 3.20; 95% CI = 1.16-8.86). CONCLUSION: Among older Black adults, APOL1 highrisk genotypes were associated with lower kidney function and therefore higher risk of ESRD. Racial disparities in incident kidney disease persisted in older age and were not fully explained by APOL1.

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“…Apolipoprotein L1 (APOL1) is located at chromosome 22q12.3 and APOL1 gene encodes a trypanolytic factor that dissolves pathogenic Trypanosoma brucei subspecies in humans and gorillas ( 28 ). Other studies have shown a link between non-diabetic nephropathy and variations in the APOL1 gene ( 29 , 30 ), which are also associated with atherosclerosis ( 31 ). APOL1 is one of six genes of the APOL gene family, which are a set of genomic hotspots for various diseases ( 32 ), including schizophrenia, cancer and chronic kidney disease ( 33 , 34 ).…”

Section: Introductionmentioning

confidence: 99%

The clinical significance of apolipoprotein L1 in head and neck squamous cell carcinoma

Zhong¹,

Chen

et al. 2020

Oncol Lett

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Approximately 500,000 new head and neck squamous cell carcinoma (HNSCC) cases are detected every year around the world, and its incidence ranks sixth among all cancer types globally. Among these cases, oral squamous cell carcinoma (OSCC) and laryngeal squamous cell carcinoma (LSCC) are HNSCC subtypes with high incidence rates, especially in China. The present study examines the association between the apolipoprotein L1 (APOL1) mRNA and protein expression and clinical parameters in HNSCC. The two most common types (oral and larynx) of HNSCC were selected for subgroup analyses. Immunohistochemistry (IHC) was used to detect APOL1 protein expression levels in HNSCC clinical specimens. It was demonstrated that APOL1 protein expression in 221 cases of HNSCC was higher compared with that in normal tissues. Consistent upregulation of APOL1 protein was also found in subgroups of OSCC and LSCC. Through mining the ArrayExpress, The Cancer Genome Atlas and the Gene Expression Omnibus databases, microarrays and RNA sequencing data for HNSCC were retrieved, which were used to analyze APOL1 mRNA expression levels. The results showed that APOL1 expression was higher in both OSCC and LSCC subtypes, as well as in HNSCC, compared with that in non-cancerous squamous epithelium. The summary receiver operating characteristic analysis showed that APOL1 had potential as a diagnostic biomarker for HNSCC, OSCC and LSCC. Thus, upregulation of APOL1 may contribute to the tumorigenesis of HNSCC.

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Association of APOL1 With Heart Failure With Preserved Ejection Fraction in Postmenopausal African American Women

Cited by 15 publications

References 47 publications

Hypertensive APOL1 risk allele carriers demonstrate greater blood pressure reduction with angiotensin receptor blockade compared to low risk carriers

Hypertensive APOL1 risk allele carriers demonstrate greater blood pressure reduction with angiotensin receptor blockade compared to low risk carriers

Race, APOL1 Risk Variants, and Clinical Outcomes among Older Adults: The ARIC Study

The clinical significance of apolipoprotein L1 in head and neck squamous cell carcinoma

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