Association Between the APOE*4 Allele and Atherosclerosis Is Age Dependent Among Argentine Males

Bañares, V.; Peterson, Graciela; Aguilar, Daniel; Gulayin, Ricardo; Sisu, Elías; Wyszynski, Diego F.; Pivetta, Omar H.; Tavella, Marcelo

doi:10.1353/hub.2005.0036

Cited by 9 publications

(9 citation statements)

References 21 publications

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“…We divided the cohort into four age groups representing decades of older adulthood in order to account for differences in APOE ε4 risk by age . Demographic data for the entire cohort and each of the four subgroups are summarized in Table .…”

Section: Resultsmentioning

confidence: 99%

“…Of the known common genetic risk factors for AD, carrying the ε4 allele of apolipoprotein E ( APOE) is the strongest predictor of AD risk and has been shown to moderate amyloid‐related memory decline in preclinical AD . Retrospective studies indicate that APOE ε4 modifies risk in an age‐dependent manner in AD and other diseases, including cardiovascular disease . However, it is unknown whether APOE ε4 has age‐dependent effects among cognitively normal older individuals in the earliest stages of AD.…”

Section: Introductionmentioning

confidence: 99%

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Age‐dependent effects of APOE ε4 in preclinical Alzheimer's disease

Bonham

Geier

Fan

et al. 2016

Ann Clin Transl Neurol

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ObjectiveThe ε4 allele of apolipoprotein E (APOE) is the strongest known common genetic risk factor for Alzheimer's disease (AD) and alters age of onset in retrospective studies. Here, we longitudinally test the effects of APOE ε4 genotype and age during progression from normal cognition to AD.MethodsUsing data from 5381 cognitively normal older individuals and Cox proportional hazards models, we longitudinally tested the effects of APOE genotype on progression from normal cognition to mild cognitive impairment (MCI) or AD in four age strata (<60, 60–70, 70–80, 80 + ) and with a sliding window approach between ages 60 and 85.ResultsWe found that APOE ε4 carrier status and dosage significantly influenced progression to MCI or AD in all four age groups and that APOE ε4‐associated progression risk peaked between ages 70 and 75. We confirmed APOE ε4‐associated progression risk in a subset of the cohort with pathologically proven diagnoses.InterpretationOur findings indicate that in clinically normal individuals, APOE ε4 status significantly predicts progression to MCI or AD across older adulthood and that this risk varies with age. This information will be useful as therapeutic interventions become available and clinical decisions can be individually tailored based on age and genetic data.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Age‐dependent effects of APOE ε4 in preclinical Alzheimer's disease

Bonham

Geier

Fan

et al. 2016

Ann Clin Transl Neurol

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“…Minor molecular change has profound pathological consequences. While E3 allele codes for wild-type protein (Cys 112 /Arg 158 ), E2 (Cys 112 /Cys 158 ) is associated with type III hyperlipoproteinemia (HPL III), and allele E4 (Arg 112 /Arg 158 ) has been implicated in atherosclerosis [ 90 , 91 ].…”

Section: Genetic Variants In Lipoprotein Metabolismmentioning

confidence: 99%

Genetic Variation and Atherosclerosis

Biroš

Karan²,

Golledge³

2008

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A family history of atherosclerosis is independently associated with an increased incidence of cardiovascular events. The genetic factors underlying the importance of inheritance in atherosclerosis are starting to be understood. Genetic variation, such as mutations or common polymorphisms has been shown to be involved in modulation of a range of risk factors, such as plasma lipoprotein levels, inflammation and vascular calcification. This review presents examples of present studies of the role of genetic polymorphism in atherosclerosis.

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“…While ε3 (wild type) and ε4 isoforms are recognized by their LDL receptors, the ε2 isoform displays extremely low binding affinity and is associated with type III hyperlipidemia [14]. The ε4 isoform has been implicated in atherosclerosis [9,10,15]. To our knowledge the association of ApoE genotype with AAA presence has not been previously examined in a large cohort.…”

Section: Introductionmentioning

confidence: 99%

Apolipoprotein E genotype is associated with serum C-reactive protein but not abdominal aortic aneurysm

et al. 2010

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Objective Apolipoprotein E (ApoE) genotype has been associated with systemic inflammation and athero-thrombosis however the association with abdominal aortic aneurysm (AAA) has not been previously examined. We assessed the association between ApoE genotype with AAA presence and growth, and serum C-reactive protein (CRP). Methods Serum concentrations of CRP (in 1358 men) and 6 single nucleotide polymorphisms (SNPs) for ApoE (in 1711 men) were examined in subjects from the Health In Men Study. 640 men with small AAAs were followed by ultrasound surveillance for a mean of 4.1 years. Results There was no association between ApoE genotype and AAA presence. Men heterozygote for the ApoE p.Arg176Cys polymorphism had slower AAA growth, odds ratio for AAA progression ≥ median 0.41, 95% confidence intervals 0.21-0.80, p=0.01. Men heterozygote for the ApoE g.50093756A>G polymorphism had slightly more rapid AAA growth, odds ratio for AAA progression ≥ median 1.48, 95% confidence intervals 1.02-2.14, p=0.04. None of the ApoE SNPs were associated with AAA growth however taking into account multiple testing. Two SNPs in ApoE were associated with serum CRP under a co-dominant model, ApoE p.Cys130Arg (SNP ID rs429358), p=0.00003 and ApoE g.50114786A>G (SNP ID rs4420638), p=0.00013. Adjusting for other risk factors plus serum creatinine the ε4 allele was associated with lower serum CRP under a dominant model, coefficient 0.089, p=0.002. Conclusion We found no consistent association between ApoE genotype and AAA. We confirmed an association between ApoE genotype and serum CRP.

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Association Between the APOE*4 Allele and Atherosclerosis Is Age Dependent Among Argentine Males

Cited by 9 publications

References 21 publications

Age‐dependent effects of APOE ε4 in preclinical Alzheimer's disease

Age‐dependent effects of APOE ε4 in preclinical Alzheimer's disease

Genetic Variation and Atherosclerosis

Apolipoprotein E genotype is associated with serum C-reactive protein but not abdominal aortic aneurysm

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