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Plasma apoM and S1P levels are inversely associated with mortality in African Americans with type 2 diabetes mellitus.
Liu M, Frej C, Langefeld CD, Divers J, Bowden DW, Carr JJ, Gebre AK, Xu J, Larsson B, Dahlbäck B, Freedman BI, Parks JS
(2019) J Lipid Res 60: 1425-1431
MeSH Terms: African Americans, Apolipoproteins M, Biomarkers, Diabetes Mellitus, Type 2, Disease-Free Survival, Female, Humans, Lysophospholipids, Male, Middle Aged, Sphingosine, Survival Rate
Show Abstract · Added January 10, 2020
apoM is a minor HDL apolipoprotein and carrier for sphingosine-1-phosphate (S1P). HDL apoM and S1P concentrations are inversely associated with atherosclerosis progression in rodents. We evaluated associations between plasma concentrations of S1P, plasma concentrations of apoM, and HDL apoM levels with prevalent subclinical atherosclerosis and mortality in the African American-Diabetes Heart Study participants (N = 545). Associations between plasma S1P, plasma apoM, and HDL apoM with subclinical atherosclerosis and mortality were assessed using multivariate parametric, nonparametric, and Cox proportional hazards models. At baseline, participants' median (25th percentile, 75th percentile) age was 55 (49, 62) years old and their coronary artery calcium (CAC) mass score was 26.5 (0.0, 346.5). Plasma S1P, plasma apoM, and HDL apoM were not associated with CAC. After 64 (57.6, 70.3) months of follow-up, 81 deaths were recorded. Higher concentrations of plasma S1P [odds ratio (OR) = 0.14, = 0.01] and plasma apoM (OR = 0.10, = 0.02), but not HDL apoM ( = 0.89), were associated with lower mortality after adjusting for age, sex, statin use, CAC, kidney function, and albuminuria. We conclude that plasma S1P and apoM concentrations are inversely and independently associated with mortality, but not CAC, in African Americans with type 2 diabetes after accounting for conventional risk factors.
Copyright © 2019 Liu et al.
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12 MeSH Terms
Myeloid-Specific Deletion of Epsins 1 and 2 Reduces Atherosclerosis by Preventing LRP-1 Downregulation.
Brophy ML, Dong Y, Tao H, Yancey PG, Song K, Zhang K, Wen A, Wu H, Lee Y, Malovichko MV, Sithu SD, Wong S, Yu L, Kocher O, Bischoff J, Srivastava S, Linton MF, Ley K, Chen H
(2019) Circ Res 124: e6-e19
MeSH Terms: Adaptor Proteins, Vesicular Transport, Animals, Apolipoproteins E, Atherosclerosis, Cells, Cultured, Down-Regulation, Gene Deletion, HEK293 Cells, Humans, Low Density Lipoprotein Receptor-Related Protein-1, Macrophages, Mice, Myeloid Cells, RAW 264.7 Cells, Receptors, LDL, Tumor Suppressor Proteins, Ubiquitination
Show Abstract · Added April 10, 2019
RATIONALE - Atherosclerosis is, in part, caused by immune and inflammatory cell infiltration into the vascular wall, leading to enhanced inflammation and lipid accumulation in the aortic endothelium. Understanding the molecular mechanisms underlying this disease is critical for the development of new therapies. Our recent studies demonstrate that epsins, a family of ubiquitin-binding endocytic adaptors, are critical regulators of atherogenicity. Given the fundamental contribution lesion macrophages make to fuel atherosclerosis, whether and how myeloid-specific epsins promote atherogenesis is an open and significant question.
OBJECTIVE - We will determine the role of myeloid-specific epsins in regulating lesion macrophage function during atherosclerosis.
METHODS AND RESULTS - We engineered myeloid cell-specific epsins double knockout mice (LysM-DKO) on an ApoE background. On Western diet, these mice exhibited marked decrease in atherosclerotic lesion formation, diminished immune and inflammatory cell content in aortas, and reduced necrotic core content but increased smooth muscle cell content in aortic root sections. Epsins deficiency hindered foam cell formation and suppressed proinflammatory macrophage phenotype but increased efferocytosis and anti-inflammatory macrophage phenotype in primary macrophages. Mechanistically, we show that epsin loss specifically increased total and surface levels of LRP-1 (LDLR [low-density lipoprotein receptor]-related protein 1), an efferocytosis receptor with antiatherosclerotic properties. We further show that epsin and LRP-1 interact via epsin's ubiquitin-interacting motif domain. ox-LDL (oxidized LDL) treatment increased LRP-1 ubiquitination, subsequent binding to epsin, and its internalization from the cell surface, suggesting that epsins promote the ubiquitin-dependent internalization and downregulation of LRP-1. Crossing ApoE/LysM-DKO mice onto an LRP-1 heterozygous background restored, in part, atherosclerosis, suggesting that epsin-mediated LRP-1 downregulation in macrophages plays a pivotal role in propelling atherogenesis.
CONCLUSIONS - Myeloid epsins promote atherogenesis by facilitating proinflammatory macrophage recruitment and inhibiting efferocytosis in part by downregulating LRP-1, implicating that targeting epsins in macrophages may serve as a novel therapeutic strategy to treat atherosclerosis.
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17 MeSH Terms
Clinical Genetic Testing for Familial Hypercholesterolemia: JACC Scientific Expert Panel.
Sturm AC, Knowles JW, Gidding SS, Ahmad ZS, Ahmed CD, Ballantyne CM, Baum SJ, Bourbon M, Carrié A, Cuchel M, de Ferranti SD, Defesche JC, Freiberger T, Hershberger RE, Hovingh GK, Karayan L, Kastelein JJP, Kindt I, Lane SR, Leigh SE, Linton MF, Mata P, Neal WA, Nordestgaard BG, Santos RD, Harada-Shiba M, Sijbrands EJ, Stitziel NO, Yamashita S, Wilemon KA, Ledbetter DH, Rader DJ, Convened by the Familial Hypercholesterolemia Foundation
(2018) J Am Coll Cardiol 72: 662-680
MeSH Terms: Apolipoproteins B, Expert Testimony, Genetic Counseling, Genetic Testing, Humans, Hyperlipoproteinemia Type II, Proprotein Convertase 9, Receptors, LDL
Show Abstract · Added April 10, 2019
Although awareness of familial hypercholesterolemia (FH) is increasing, this common, potentially fatal, treatable condition remains underdiagnosed. Despite FH being a genetic disorder, genetic testing is rarely used. The Familial Hypercholesterolemia Foundation convened an international expert panel to assess the utility of FH genetic testing. The rationale includes the following: 1) facilitation of definitive diagnosis; 2) pathogenic variants indicate higher cardiovascular risk, which indicates the potential need for more aggressive lipid lowering; 3) increase in initiation of and adherence to therapy; and 4) cascade testing of at-risk relatives. The Expert Consensus Panel recommends that FH genetic testing become the standard of care for patients with definite or probable FH, as well as for their at-risk relatives. Testing should include the genes encoding the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9); other genes may also need to be considered for analysis based on patient phenotype. Expected outcomes include greater diagnoses, more effective cascade testing, initiation of therapies at earlier ages, and more accurate risk stratification.
Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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8 MeSH Terms
Sex-specific genetic predictors of Alzheimer's disease biomarkers.
Deming Y, Dumitrescu L, Barnes LL, Thambisetty M, Kunkle B, Gifford KA, Bush WS, Chibnik LB, Mukherjee S, De Jager PL, Kukull W, Huentelman M, Crane PK, Resnick SM, Keene CD, Montine TJ, Schellenberg GD, Haines JL, Zetterberg H, Blennow K, Larson EB, Johnson SC, Albert M, Moghekar A, Del Aguila JL, Fernandez MV, Budde J, Hassenstab J, Fagan AM, Riemenschneider M, Petersen RC, Minthon L, Chao MJ, Van Deerlin VM, Lee VM, Shaw LM, Trojanowski JQ, Peskind ER, Li G, Davis LK, Sealock JM, Cox NJ, Alzheimer’s Disease Neuroimaging Initiative (ADNI), Alzheimer Disease Genetics Consortium (ADGC), Goate AM, Bennett DA, Schneider JA, Jefferson AL, Cruchaga C, Hohman TJ
(2018) Acta Neuropathol 136: 857-872
MeSH Terms: Aged, 80 and over, Alzheimer Disease, Amyloid beta-Peptides, Amyloidosis, Apolipoproteins E, Biomarkers, Brain, Claudins, Female, Genome-Wide Association Study, Genotype, Humans, Male, Muscle Proteins, Mutation, Peptide Fragments, Serpins, Sex Factors, Transcription Factors, tau Proteins
Show Abstract · Added March 26, 2019
Cerebrospinal fluid (CSF) levels of amyloid-β 42 (Aβ42) and tau have been evaluated as endophenotypes in Alzheimer's disease (AD) genetic studies. Although there are sex differences in AD risk, sex differences have not been evaluated in genetic studies of AD endophenotypes. We performed sex-stratified and sex interaction genetic analyses of CSF biomarkers to identify sex-specific associations. Data came from a previous genome-wide association study (GWAS) of CSF Aβ42 and tau (1527 males, 1509 females). We evaluated sex interactions at previous loci, performed sex-stratified GWAS to identify sex-specific associations, and evaluated sex interactions at sex-specific GWAS loci. We then evaluated sex-specific associations between prefrontal cortex (PFC) gene expression at relevant loci and autopsy measures of plaques and tangles using data from the Religious Orders Study and Rush Memory and Aging Project. In Aβ42, we observed sex interactions at one previous and one novel locus: rs316341 within SERPINB1 (p = 0.04) and rs13115400 near LINC00290 (p = 0.002). These loci showed stronger associations among females (β = - 0.03, p = 4.25 × 10; β = 0.03, p = 3.97 × 10) than males (β = - 0.02, p = 0.009; β = 0.01, p = 0.20). Higher levels of expression of SERPINB1, SERPINB6, and SERPINB9 in PFC was associated with higher levels of amyloidosis among females (corrected p values < 0.02) but not males (p > 0.38). In total tau, we observed a sex interaction at a previous locus, rs1393060 proximal to GMNC (p = 0.004), driven by a stronger association among females (β = 0.05, p = 4.57 × 10) compared to males (β = 0.02, p = 0.03). There was also a sex-specific association between rs1393060 and tangle density at autopsy (p = 0.047; p = 0.96), and higher levels of expression of two genes within this locus were associated with lower tangle density among females (OSTN p = 0.006; CLDN16 p = 0.002) but not males (p ≥ 0.32). Results suggest a female-specific role for SERPINB1 in amyloidosis and for OSTN and CLDN16 in tau pathology. Sex-specific genetic analyses may improve understanding of AD's genetic architecture.
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20 MeSH Terms
Sex-Specific Association of Apolipoprotein E With Cerebrospinal Fluid Levels of Tau.
Hohman TJ, Dumitrescu L, Barnes LL, Thambisetty M, Beecham G, Kunkle B, Gifford KA, Bush WS, Chibnik LB, Mukherjee S, De Jager PL, Kukull W, Crane PK, Resnick SM, Keene CD, Montine TJ, Schellenberg GD, Haines JL, Zetterberg H, Blennow K, Larson EB, Johnson SC, Albert M, Bennett DA, Schneider JA, Jefferson AL, Alzheimer’s Disease Genetics Consortium and the Alzheimer’s Disease Neuroimaging Initiative
(2018) JAMA Neurol 75: 989-998
MeSH Terms: Aged, 80 and over, Alzheimer Disease, Amyloid beta-Peptides, Apolipoproteins E, Cohort Studies, Female, Genotype, Humans, Male, Neurofibrillary Tangles, Peptide Fragments, Phosphoproteins, Plaque, Amyloid, Sex Factors, tau Proteins
Show Abstract · Added March 26, 2019
Importance - The strongest genetic risk factor for Alzheimer disease (AD), the apolipoprotein E (APOE) gene, has a stronger association among women compared with men. Yet limited work has evaluated the association between APOE alleles and markers of AD neuropathology in a sex-specific manner.
Objective - To evaluate sex differences in the association between APOE and markers of AD neuropathology measured in cerebrospinal fluid (CSF) during life or in brain tissue at autopsy.
Design, Setting, and Participants - This multicohort study selected data from 10 longitudinal cohort studies of normal aging and AD. Cohorts had variable recruitment criteria and follow-up intervals and included population-based and clinic-based samples. Inclusion in our analysis required APOE genotype data and either CSF data available for analysis. Analyses began on November 6, 2017, and were completed on December 20, 2017.
Main Outcomes and Measures - Biomarker analyses included levels of β-amyloid 42, total tau, and phosphorylated tau measured in CSF. Autopsy analyses included Consortium to Establish a Registry for Alzheimer's Disease staging for neuritic plaques and Braak staging for neurofibrillary tangles.
Results - Of the 1798 patients in the CSF biomarker cohort, 862 were women, 226 had AD, 1690 were white, and the mean (SD) age was 70 [9] years. Of the 5109 patients in the autopsy cohort, 2813 were women, 4953 were white, and the mean (SD) age was 84 (9) years. After correcting for multiple comparisons using the Bonferroni procedure, we observed a statistically significant interaction between APOE-ε4 and sex on CSF total tau (β = 0.41; 95% CI, 0.27-0.55; P < .001) and phosphorylated tau (β = 0.24; 95% CI, 0.09-0.38; P = .001), whereby APOE showed a stronger association among women compared with men. Post hoc analyses suggested this sex difference was present in amyloid-positive individuals (β = 0.41; 95% CI, 0.20-0.62; P < .001) but not among amyloid-negative individuals (β = 0.06; 95% CI, -0.18 to 0.31; P = .62). We did not observe sex differences in the association between APOE and β-amyloid 42, neuritic plaque burden, or neurofibrillary tangle burden.
Conclusions and Relevance - We provide robust evidence of a stronger association between APOE-ε4 and CSF tau levels among women compared with men across multiple independent data sets. Interestingly, APOE-ε4 is not differentially associated with autopsy measures of neurofibrillary tangles. Together, the sex difference in the association between APOE and CSF measures of tau and the lack of a sex difference in the association with neurofibrillary tangles at autopsy suggest that APOE may modulate risk for neurodegeneration in a sex-specific manner, particularly in the presence of amyloidosis.
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15 MeSH Terms
APOE genotype modifies the association between central arterial stiffening and cognition in older adults.
Cambronero FE, Liu D, Neal JE, Moore EE, Gifford KA, Terry JG, Nair S, Pechman KR, Osborn KE, Hohman TJ, Bell SP, Sweatt JD, Wang TJ, Beckman JA, Carr JJ, Jefferson AL
(2018) Neurobiol Aging 67: 120-127
MeSH Terms: Aged, Aged, 80 and over, Aging, Alzheimer Disease, Apolipoproteins E, Cognition, Cognitive Dysfunction, Female, Genetic Association Studies, Genotype, Humans, Magnetic Resonance Imaging, Male, Pulse Wave Analysis, Risk Factors, Vascular Stiffness
Show Abstract · Added September 11, 2018
Arterial stiffening is associated with cognitive impairment and prodromal Alzheimer's disease. This study tested the interaction between arterial stiffening and an Alzheimer's disease genetic risk factor (apolipoprotein E [APOE] genotype) on cognition among older adults. Vanderbilt Memory & Aging Project participants with normal cognition (n = 162, 72 ± 7 years, 29% APOE-ε4 carrier) and mild cognitive impairment (n = 121, 73 ± 8 years, 42% APOE-ε4 carrier) completed neuropsychological assessment and cardiac MRI to assess aortic stiffening using pulse wave velocity (PWV, m/s). Linear regression models stratified by cognitive diagnosis related aortic PWV × APOE-ε4 status to neuropsychological performances, adjusting for demographic and vascular risk factors. PWV × APOE-ε4 related to poorer performance on measures of lexical retrieval (β = -0.29, p = 0.01), executive function (β = -0.44, p = 0.02), and episodic memory (β = -3.07, p = 0.02). Among participants with higher aortic PWV, APOE-ε4 modified the association between central arterial stiffening and cognition, such that carriers had worse performances than noncarriers. Findings add to a growing body of evidence for APOE-vascular interactions on cognition in older adults and warrant further research into less heart-healthy cohorts where the association between PWV and cognition among older adults might be stronger.
Copyright © 2018 Elsevier Inc. All rights reserved.
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16 MeSH Terms
APOE allele frequencies in suspected non-amyloid pathophysiology (SNAP) and the prodromal stages of Alzheimer's Disease.
Hohman TJ, Dumitrescu L, Oksol A, Wagener M, Gifford KA, Jefferson AL, Alzheimer’s Disease Neuroimaging Initiative
(2017) PLoS One 12: e0188501
MeSH Terms: Aged, Alzheimer Disease, Amyloid beta-Peptides, Apolipoproteins E, Biomarkers, Brain, Female, Gene Frequency, Humans, Magnetic Resonance Imaging, Male, Prodromal Symptoms
Show Abstract · Added March 16, 2018
Biomarker definitions for preclinical Alzheimer's disease (AD) have identified individuals with neurodegeneration (ND+) without β-amyloidosis (Aβ-) and labeled them with suspected non-AD pathophysiology (SNAP). We evaluated Apolipoprotein E (APOE) ε2 and ε4 allele frequencies across biomarker definitions-Aβ-/ND- (n = 268), Aβ+/ND- (n = 236), Aβ-/ND+ or SNAP (n = 78), Aβ+/ND+ (n = 204)-hypothesizing that SNAP would have an APOE profile comparable to Aβ-/ND-. Using AD Neuroimaging Initiative data (n = 786, 72±7 years, 48% female), amyloid status (Aβ+ or Aβ-) was defined by cerebrospinal fluid (CSF) Aβ-42 levels, and neurodegeneration status (ND+ or ND-) was defined by hippocampal volume from MRI. Binary logistic regression related biomarker status to APOE ε2 and ε4 allele carrier status, adjusting for age, sex, education, and cognitive diagnosis. Compared to the biomarker negative (Aβ-/ND-) participants, higher proportions of ε4 and lower proportions of ε2 carriers were observed among Aβ+/ND- (ε4: OR = 6.23, p<0.001; ε2: OR = 0.53, p = 0.03) and Aβ+/ND+ participants (ε4: OR = 12.07, p<0.001; ε2: OR = 0.29, p = 0.004). SNAP participants were statistically comparable to biomarker negative participants (p-values>0.30). In supplemental analyses, comparable results were observed when coding SNAP using amyloid imaging and when using CSF tau levels. In contrast to APOE, a polygenic risk score for AD that excluded APOE did not show an association with amyloidosis or neurodegeneration (p-values>0.15), but did show an association with SNAP defined using CSF tau (β = 0.004, p = 0.02). Thus, in a population with low levels of cerebrovascular disease and a lower prevalence of SNAP than the general population, APOE and known genetic drivers of AD do not appear to contribute to the neurodegeneration observed in SNAP. Additional work in population based samples is needed to better elucidate the genetic contributors to various etiological drivers of SNAP.
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12 MeSH Terms
Amyloid Accumulation Drives Proteome-wide Alterations in Mouse Models of Alzheimer's Disease-like Pathology.
Savas JN, Wang YZ, DeNardo LA, Martinez-Bartolome S, McClatchy DB, Hark TJ, Shanks NF, Cozzolino KA, Lavallée-Adam M, Smukowski SN, Park SK, Kelly JW, Koo EH, Nakagawa T, Masliah E, Ghosh A, Yates JR
(2017) Cell Rep 21: 2614-2627
MeSH Terms: Alzheimer Disease, Amyloid beta-Peptides, Animals, Apolipoproteins E, Brain, Calcium Channels, Computational Biology, Female, Mass Spectrometry, Mice, Mice, Inbred C57BL, Proteome
Show Abstract · Added March 21, 2018
Amyloid beta (Aβ) peptides impair multiple cellular pathways and play a causative role in Alzheimer's disease (AD) pathology, but how the brain proteome is remodeled by this process is unknown. To identify protein networks associated with AD-like pathology, we performed global quantitative proteomic analysis in three mouse models at young and old ages. Our analysis revealed a robust increase in Apolipoprotein E (ApoE) levels in nearly all brain regions with increased Aβ levels. Taken together with prior findings on ApoE driving Aβ accumulation, this analysis points to a pathological dysregulation of the ApoE-Aβ axis. We also found dysregulation of protein networks involved in excitatory synaptic transmission. Analysis of the AMPA receptor (AMPAR) complex revealed specific loss of TARPγ-2, a key AMPAR-trafficking protein. Expression of TARPγ-2 in hAPP transgenic mice restored AMPA currents. This proteomic database represents a resource for the identification of protein alterations responsible for AD.
Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
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12 MeSH Terms
Loss of SPRR3 in ApoE-/- mice leads to atheroma vulnerability through Akt dependent and independent effects in VSMCs.
Lietman CD, Segedy AK, Li B, Fazio S, Atkinson JB, Linton MF, Young PP
(2017) PLoS One 12: e0184620
MeSH Terms: Animals, Apolipoproteins E, Cornified Envelope Proline-Rich Proteins, Female, Fibronectins, Immunoblotting, Mice, Mice, Inbred C57BL, Mice, Knockout, Muscle, Smooth, Vascular, Myocytes, Smooth Muscle, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt, Real-Time Polymerase Chain Reaction, Signal Transduction
Show Abstract · Added April 10, 2018
Vascular smooth muscle cells (VSMCs) represent important modulators of plaque stability in advanced lesions. We previously reported that loss of small proline-rich repeat protein 3 (Sprr3), leads to VSMC apoptosis in a PI3K/Akt-dependent manner and accelerates lesion progression. Here, we investigated the role of Sprr3 in modulating plaque stability in hyperlipidemic ApoE-/- mice. We show that loss of Sprr3 increased necrotic core size and reduced cap collagen content of atheromas in brachiocephalic arteries with evidence of plaque rupture and development of intraluminal thrombi. Moreover, Sprr3-/-ApoE-/- mice developed advanced coronary artery lesions accompanied by intraplaque hemorrhage and left ventricle microinfarcts. SPRR3 is known to reduce VSMC survival in lesions by promoting their apoptosis. In addition, we demonstrated that Sprr3-/- VSMCs displayed reduced expression of procollagen in a PI3K/Akt dependent manner. SPRR3 loss also increased MMP gelatinase activity in lesions, and increased MMP2 expression, migration and contraction of VSMCs independently of PI3K/Akt. Consequently, Sprr3 represents the first described VSMC modulator of each of the critical features of cap stability, including VSMC numbers, collagen type I synthesis, and protease activity through Akt dependent and independent pathways.
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MeSH Terms
Apolipoprotein L1 Variants and Blood Pressure Traits in African Americans.
Nadkarni GN, Galarneau G, Ellis SB, Nadukuru R, Zhang J, Scott SA, Schurmann C, Li R, Rasmussen-Torvik LJ, Kho AN, Hayes MG, Pacheco JA, Manolio TA, Chisholm RL, Roden DM, Denny JC, Kenny EE, Bottinger EP
(2017) J Am Coll Cardiol 69: 1564-1574
MeSH Terms: Adult, African Americans, Aged, Apolipoprotein L1, Apolipoproteins, Blood Pressure, Cohort Studies, Female, Humans, Hypertension, Lipoproteins, HDL, Male, Middle Aged, Young Adult
Show Abstract · Added March 14, 2018
BACKGROUND - African Americans (AA) are disproportionately affected by hypertension-related health disparities. Apolipoprotein L1 (APOL1) risk variants are associated with kidney disease in hypertensive AAs.
OBJECTIVES - This study assessed the APOL1 risk alleles' association with blood pressure traits in AAs.
METHODS - The discovery cohort included 5,204 AA participants from Mount Sinai's BioMe biobank. Replication cohorts included additional BioMe (n = 1,623), Vanderbilt BioVU (n = 1,809), and Northwestern NUgene (n = 567) AA biobank participants. Single nucleotide polymorphisms determining APOL1 G1 and G2 risk alleles were genotyped in BioMe and imputed in BioVU/NUgene participants. APOL1 risk alleles' association with blood pressure-related traits was tested in the discovery cohort, a meta-analysis of replication cohorts, and a combined meta-analysis under recessive and additive models after adjusting for age, sex, body mass index, and estimated glomerular filtration rate.
RESULTS - There were 14% to 16% of APOL1 variant allele homozygotes (2 copies of G1/G2) across cohorts. APOL1 risk alleles were associated under an additive model with systolic blood pressure (SBP) and age at diagnosis of hypertension, which was 2 to 5 years younger in the APOL1 variant allele homozygotes (Cox proportional hazards analysis, p value for combined meta-analysis [p] = 1.9 × 10). APOL1 risk alleles were associated with overall SBP (p = 7.0 × 10) and diastolic blood pressure (p = 2.8 × 10). After adjustment for all covariates, those in the 20- to 29-year age range showed an increase in SBP of 0.94 ± 0.44 mm Hg (p = 0.01) per risk variant copy. APOL1-associated estimated glomerular filtration rate decline was observed starting a decade later in life in the 30- to 39-year age range.
CONCLUSIONS - APOL1 risk alleles are associated with higher SBP and earlier hypertension diagnoses in young AAs; this relationship appears to follow an additive model.
Copyright © 2017 American College of Cardiology Foundation. All rights reserved.
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14 MeSH Terms