APOL1 Risk Alleles, Cardiac Markers, and Risk of ESKD in African Americans: The Atherosclerosis Risk in Communities Study.
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ABSTRACT:
SUBMITTER: Surapaneni AL
PROVIDER: S-EPMC7406838 | biostudies-literature | 2020 Jul-Aug
REPOSITORIES: biostudies-literature
Publications
<i>APOL1</i> Risk Alleles, Cardiac Markers, and Risk of ESKD in African Americans: The Atherosclerosis Risk in Communities Study.
Surapaneni Aditya L AL Ballew Shoshana H SH Coresh Josef J Ballantyne Christie M CM Selvin Elizabeth E Matsushita Kunihiro K Grams Morgan E ME
Kidney medicine 20200522 4
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Project description:In an entirely African-American cohort, we compared clinical characteristics, cardiac structure and function, and all-cause mortality in patients with heart failure (HF) with preserved ejection fraction (HFpEF) in relation to patients with heart failure with reduced ejection fraction (HFrEF) and those without HF.African Americans are at increased risk for HF. Nevertheless, there are limited phenotypic and prognostic data in African Americans with HFpEF compared with those with HFrEF and those without HF.Middle-aged African Americans from the Jackson, Mississippi, cohort of the ARIC (Atherosclerosis Risk In Communities) study (n = 2,445) underwent echocardiography between 1993 and 1995. HF prevalence was available in 1,962 patients for whom left ventricular ejection fraction (LVEF) could be quantified. Participants with HF were categorized as having HFpEF (LVEF ≥50%), HFrEF (LVEF <50%), or no HF, with comparisons made between groups.HF was identified in 116 (5.9%) participants (HFpEF n = 85 [73%]; HFrEF n = 31 [27%]). Compared with those without HF, those with HFpEF were older, were more likely to be female, and had more frequent comorbidities and concentric hypertrophy. In relation to HFrEF, those with HFpEF were more likely to be female but less likely to have coronary heart disease, diabetes mellitus, chronic kidney disease, left atrial enlargement, and eccentric hypertrophy. Over a median 13.7 years of follow-up, risk of death differed between groups, with age- and sex-adjusted hazard ratios of 1.51 (95% confidence interval: 1.01 to 2.25) for HFpEF versus those without HF and 2.50 (95% confidence interval: 1.37 to 4.58) for HFrEF versus HFpEF.In this cohort of middle-aged African Americans, HFpEF was the most common form of HF and was associated with a substantially better prognosis than HFrEF but worse than those without HF.
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Project description:African Americans have a 2- to 4-fold greater incidence of end-stage kidney disease (ESKD) than whites, which has long raised the possibility of a genetic cause for this disparity. Recent advances in genetic studies have shown a causal association of polymorphisms at the apolipoprotein L1 gene (APOL1) with the markedly increased risk for the nondiabetic component of the overall disparity in ESKD in African Americans. Although APOL1-associated kidney disease is thought to account for a substantial proportion of ESKD in African Americans, not all the increased risk for ESKD is accounted for, and a complete cataloging of disparities in genetic causes of ESKD eludes our current understanding of genetic-associated kidney disease. Genetic testing aids the screening, diagnosis, prognosis, and treatment of diseases with a genetic basis. Widespread use of genetic testing in clinical practice is limited by the small number of actionable genetic variants, limited health literacy of providers and patients, and underlying complex ethical, legal, and social issues. This perspective reviews racial and ethnic differences associated with genetic diseases and the development of ESKD in African Americans and discusses potential uncertainties associated with our current understanding of penetrance of genetically linked kidney disease and population-attributable risk percent.
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Project description: Not available
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Project description:Although case-control studies suggest that African Americans with common coding variants in the APOL1 gene are 5-29 times more likely than those individuals without such variants to have focal segmental glomerulosclerosis, HIV-associated nephropathy, or ESRD, prospective studies have not yet evaluated the impact of these variants on CKD in a community-based sample of African Americans. Here, we studied whether the APOL1 G1 and G2 risk alleles associate with the development of CKD and progression to ESRD by analyzing data from 3067 African Americans in the Atherosclerosis Risk in Communities Study who did not have CKD at baseline. Carrying two risk alleles associated with a 1.49-fold increased risk of CKD (95% CI=1.02 to 2.17) and a 1.88-fold increased risk of ESRD (95% CI=1.20 to 2.93) compared with zero or one risk allele; associations persisted after adjusting for European ancestry. Among participants who developed CKD, those participants with two risk alleles were more likely to progress to ESRD than their counterparts with zero or one risk allele (HR=2.22, 95% CI=1.01 to 4.84). In conclusion, APOL1 risk variants are risk factors for the development of CKD and progression from CKD to ESRD among African Americans in the general population.
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Project description:BackgroundEffects of alcohol consumption on health and disease are complex and involve a number of cellular and metabolic processes.ObjectiveWe examined the association between alcohol consumption habits and metabolomic profiles.DesignWe conducted a cross-sectional study to explore the association of alcohol consumption habits measured by using a questionnaire with serum metabolites measured by using untargeted mass spectrometry in 1977 African Americans from the Jackson field center in the Atherosclerosis Risk in Communities Study. The whole sample was split into a discovery set (n = 1500) and a replication set (n = 477). Alcohol consumption habits were treated as an ordinal variable, with nondrinkers as the reference group and quartiles of current drinkers as ordinal groups with higher values. For each metabolite, a linear regression was conducted to estimate its relation with alcohol consumption habits separately in both sets. A modified Bonferroni procedure was used in the discovery set to adjust the significance threshold (P < 1.9 × 10⁻⁴).ResultsIn 356 named metabolites, 39 metabolites were significantly associated with alcohol consumption habits in both discovery and replication sets. In general, alcohol consumption was associated with higher levels of most metabolites such as those in amino acid and lipid pathways and with lower levels of γ-glutamyl dipeptides. Three pathways, 2-hydroxybutyrate-related metabolites, γ-glutamyl dipeptides, and lysophosphatidylcholines, which are considered to be involved in inflammation and oxidation, were associated with incident cardiovascular diseases.ConclusionsTo our knowledge, this is the largest metabolomic study thus far conducted in nonwhites. Metabolomic biomarkers of alcohol consumption were identified and replicated. The results lend new insight into potential mediating effects between alcohol consumption and future health and disease.
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Project description:Albuminuria and reduced estimated glomerular filtration rate (eGFR) associate with two apolipoprotein L1 gene (APOL1) variants in nondiabetic African Americans (AAs). Whether APOL1 associates with subclinical atherosclerosis and survival remains unclear. To determine this, 717 African American-Diabetes Heart Study participants underwent computed tomography to determine coronary artery-, carotid artery-, and aorta-calcified atherosclerotic plaque mass scores in addition to the urine albumin:creatinine ratio (UACR), eGFR, and C-reactive protein (CRP). Associations between mass scores and APOL1 were assessed adjusting for age, gender, African ancestry, body mass index (BMI), hemoglobin A1c, smoking, hypertension, use of statins and angiotensin-converting enzyme inhibitors, albuminuria, and eGFR. Participants were 58.9% female with mean age 56.5 years, eGFR 89.5 ml/min per 1.73 m(2), UACR 169.6 mg/g, and coronary artery-, carotid artery-, and aorta-calcified plaque mass scores of 610, 171, and 5378, respectively. In fully adjusted models, APOL1 risk variants were significantly associated with lower levels of carotid artery-calcified plaque (β=-0.42, s.e. 0.18; dominant model) and marginally lower coronary artery plaque (β=-0.36, s.e. 0.21; dominant model), but not with aorta-calcified plaque, CRP, UACR, or eGFR. By the end of a mean follow-up of 5.0 years, 89 participants had died. APOL1 nephropathy risk variants were significantly associated with improved survival (hazard ratio 0.67 for one copy; 0.44 for two copies). Thus, APOL1 nephropathy variants associate with lower levels of subclinical atherosclerosis and reduced risk of death in AAs with type 2 diabetes mellitus.
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