Dataset Information

Apolipoprotein L1 risk variants associate with prevalent atherosclerotic disease in African American systemic lupus erythematosus patients.

ABSTRACT: Atherosclerosis is exaggerated in African American (AA) systemic lupus erythematosus (SLE) patients, with doubled cardiovascular disease (CVD) risk compared to White patients. The extent to which common Apolipoprotein L1 (APOL1) risk alleles (RA) contribute to this trend is unknown. This retrospective cohort study assessed prevalent atherosclerotic disease across APOL1 genotypes in AA SLE patients.One hundred thirteen AA SLE subjects were APOL1-genotyped and stratified as having: zero risk alleles, one risk allele, or two risk alleles. Chart review assessed CVD manifestations including abdominal aortic aneurysm, angina, carotid artery disease, coronary artery disease, myocardial infarction, peripheral vascular disease, stroke, and vascular calcifications. Associations between the genotypes and a composite endpoint defined as one or more CVD manifestations were calculated using logistic regression. Symptomatic atherosclerotic disease, excluding incidental vascular calcifications, was also assessed.The 0-risk-allele, 1-risk-allele and 2-risk-allele groups, respectively, comprised 34%, 53%, and 13% of the cohort. Respectively, 13.2%, 41.7%, and 60.0% of the 0-risk allele, 1-risk-allele, and 2-risk-allele groups met the composite endpoint of atherosclerotic CVD (p = 0.001). Adjusting for risk factors-including smoking, ESRD, BMI >25 and hypertension-we observed an association between carrying one or more RA and atherosclerotic CVD (OR = 7.1; p = 0.002). For symptomatic disease, the OR was 3.5 (p = 0.02). In a time-to-event analysis, the proportion of subjects free from the composite primary endpoint, symptomatic atherosclerotic CVD, was higher in the 0-risk-allele group compared to the 1-risk-allele and 2-risk-allele groups (?2 = 6.5; p = 0.04).Taken together, the APOL1 RAs associate with prevalent atherosclerotic CVD in this cohort of AA SLE patients, perhaps reflecting a potentiating effect of SLE on APOL1-related cardiovascular phenotypes.

SUBMITTER: Blazer A

PROVIDER: S-EPMC5574561 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Apolipoprotein L1 risk variants associate with prevalent atherosclerotic disease in African American systemic lupus erythematosus patients.

Blazer Ashira A Wang Binhuan B Simpson Danny D Kirchhoff Tomas T Heffron Sean S Clancy Robert M RM Heguy Adriana A Ray Karina K Snuderl Matija M Buyon Jill P JP

PloS one 20170829 8

<h4>Objective</h4>Atherosclerosis is exaggerated in African American (AA) systemic lupus erythematosus (SLE) patients, with doubled cardiovascular disease (CVD) risk compared to White patients. The extent to which common Apolipoprotein L1 (APOL1) risk alleles (RA) contribute to this trend is unknown. This retrospective cohort study assessed prevalent atherosclerotic disease across APOL1 genotypes in AA SLE patients.<h4>Methods</h4>One hundred thirteen AA SLE subjects were APOL1-genotyped and str ...[more]

PMID: 28850570

Similar Datasets

Project description:Immune dysregulation in systemic lupus erythematosus (SLE) contributes to increased disease activity. African-American (AA) SLE patients have an increased prevalence of complications from disease flares and end-organ damage that leads to increased morbidity and early mortality. We previously reported alterations in inflammatory and regulatory immune mediator levels prior to disease flare in European American (EA) SLE patients. In the current study, we assessed baseline and follow-up plasma levels of 52 soluble mediators, including innate, adaptive, chemokine, and TNF superfamily members, in AA SLE patients who developed SELENA-SLEDAI defined flare 6 or 12 weeks after baseline assessment. These patients were compared to themselves during a comparable, clinically stable period (SNF, n = 18), or to demographically matched SLE patients without impending disease flare (NF, n = 13 per group). We observed significant (q < 0.05) alterations in 34 soluble mediators at baseline, with increased levels of both innate (IL-1α and type I interferons [IFN]) and adaptive cytokines (Th1-, Th2-, and Th17-type), as well as IFN-associated chemokines and soluble TNF superfamily members weeks before clinical disease flare. In contrast, stable SLE patients exhibited increased levels of the regulatory mediators IL-10 (q ≤ 0.0045) and TGF-β (q ≤ 0.0004). Because heterogeneous immune pathways were altered prior to clinical disease flare, we developed a soluble mediator score that encapsulates all mediators tested. This score is the sum of all log transformed, standardized soluble mediator levels assessed at baseline (pre-flare), weighted by their Spearman correlation coefficients for association with the SELENA-SLEDAI score at time of concurrent flare. While baseline SELENA-SLEDAI scores were similar between flare vs. NF (p = 0.7214) and SNF (p = 0.5387), the SMS was significantly higher in pre-flare SLE patients (Flare vs NF or SNF, p < 0.0001). By capturing alterations in the balance between inflammatory and regulatory mediators associated with SLE pathogenesis, the soluble mediator score approximates the immune status of SLE patients and provides a robust, predictive gauge of impending disease flare.

Project description:ObjectiveTwo apolipoprotein L1 (APOL1) risk variants (RV) are enriched in sub-Saharan African populations due to conferred resistance to Trypanosoma brucei. These variants associate with adverse renal outcomes by multiple causes including SLE. Despite emerging reports that SLE is common in Ghana, where APOL1 variant allelic frequencies are high, the regional contribution to SLE outcomes has not been described. Accordingly, this prospective longitudinal cohort study tested the associations between APOL1 high-risk genotypes and kidney outcomes, organ damage accrual and death in 100 Ghanaian patients with SLE.MethodsThis was a prospective cohort study of 100 SLE outpatients who sought care at Korle bu Teaching Hospital in Accra, Ghana. Adult patients who met 4 American College of Rheumatology criteria for SLE were genotyped for APOL1 and followed longitudinally for SLE activity as measured by the Safety of Estrogens in Lupus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) hybrid and organ injury as measured by the Systemic Lupus International Collaborating Clinics Damage Index (SDI) at baseline and every 6 months for 1 year. Outcomes of interest were kidney function, SDI and case fatality.ResultsAssuming a recessive inheritance, the APOL1 high-risk genotype (2RV) associated with end-stage renal disease (ESRD) at an OR of 14 (p=0.008). These patients accrued more SDI points particularly in renal and neurological domains. The SDI was 81.3% higher in 2RV patients compared with 0RV or 1RV patients despite no difference in SLE activity (p=0.01). After a 12-month period of observation, 3/12 (25%) of the 2RV patients died compared with 2/88 (2.3%) of the 0RV or 1RV carriers (OR=13.6, p=0.01). Deaths were due to end-stage kidney disease and heart failure.ConclusionAPOL1 RVs were heritable risk factors for morbidity and mortality in this Ghanaian SLE cohort. Despite no appreciable differences in SLE activity, APOL1 high-risk patients exhibited progressive renal disease, organ damage accrual and a 13-fold higher case fatality.

Dataset Information

Apolipoprotein L1 risk variants associate with prevalent atherosclerotic disease in African American systemic lupus erythematosus patients.

Publications

Apolipoprotein L1 risk variants associate with prevalent atherosclerotic disease in African American systemic lupus erythematosus patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets