New and confirmatory evidence of an association between APOE genotype and baseline C-reactive protein in dyslipidemic individuals

Judson, Richard S.; Brain, Carlos; Dain, Bradley; Windemuth, Andreas; Ruaño, Gualberto; Reed, Christopher Robert

doi:10.1016/j.atherosclerosis.2004.07.012

Cited by 58 publications

(48 citation statements)

References 34 publications

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“…The association between the common polymorphisms of APOE gene and the hs-CRP concentration was already reported in the elderly, 18,19 in dyslipidemic adults, 22 in type II diabetes 24 and in families. 12 However, there is no data about association between the APOE genotype and Table A1 in online appendix.…”

Section: Discussionmentioning

confidence: 72%

“…16,17 Moreover, some other gene polymorphisms were associated with circulating levels of the hs-CRP, the most studied being the common polymorphisms of the apolipoprotein E gene (APOE) (e2, e3, e4) for which an association was confirmed by many authors in adults and elderly. 12,[18][19][20][21][22][23][24] However, no data exist either about APOE genotype-hs-CRP concentration association in children or about effect of these polymorphisms in combination with estimate of heritability component. 12 Thus, in the present analysis, we aimed at reporting on (i) the association between the APOE gene alleles with the serum hs-CRP concentration in adults and also in children, (ii) the familial aggregation of the serum hs-CRP concentration on a sample of French nuclear families and on (iii) the variance-component genetic linkage of this inflammatory factor with the alleles of the APOE gene.…”

Section: Introductionmentioning

confidence: 99%

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Heritability of serum hs-CRP concentration and 5-year changes in the Stanislas family study: association with apolipoprotein E alleles

et al. 2007

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We aimed at estimating additive genetic heritability, household component effect and the influence of common alleles of the apolipoprotein E gene (APOE) on serum high-sensitivity C-reactive protein (hs-CRP) concentrations and the subsequent changes over 5 years. A sub-sample of 320 nuclear families was randomly selected from the Stanislas Family Study. Serum hs-CRP concentration was measured by immunonephelometry at entrance and after 5 years. APOE alleles were determined by restriction fragment length polymorphism. After adjustment for covariates, the number of the e4 allele was negatively associated with serum concentration of hs-CRP in the whole sample, at entrance and 5 years later, without significant interaction with sex by generation groups (P ¼ 0.003 and P ¼ 0.0003, respectively). However, no significant association was found between e4 allele and 5-year changes in hs-CRP concentration. Using a variance component analysis, no significant genetic influence was shown in family aggregation of both hs-CRP measurements and 5-year changes; the household common component was between 6.5 and 12.8%. In addition, after adjustment for APOE gene polymorphisms, degrees of resemblance were almost unchanged. In the Stanislas Family Study, e4 allele of the APOE gene was associated with lower hs-CRP concentration, but not with 5-year changes. However, variance component analysis did not evidence a significant polygenic effect.

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Section: Discussionmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 99%

Heritability of serum hs-CRP concentration and 5-year changes in the Stanislas family study: association with apolipoprotein E alleles

et al. 2007

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“…CRP, a systemic inflammatory marker, is a prominent drusen-associated molecule and is expressed in significantly higher levels among advanced AMD patients [Seddon et al, 2004]. Persons with one or two copies of ApoE E4 are associated with reduced CRP levels when compared to individuals lacking these copies [Austin et al, 2004;Judson et al, 2004;Marz et al, 2004]. This finding suggests that an ApoE isoformmediated inflammatory response may be involved in AMD etiology.…”

Section: Discussionmentioning

confidence: 99%

An apolipoprotein E variant may protect against age‐related macular degeneration through cytokine regulation

Bojanowski

Shen

Chew

et al. 2006

Environ and Mol Mutagen

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Age-related macular degeneration (AMD) is the leading cause of visual impairment and blindness among the elderly in Western countries. Genetic factors, age, cigarette smoking, nutrition, and exposure to light have been identified as AMD risk factors. In this study, we investigated the association between ApoE C112R/R158C single nucleotide polymorphisms (which determine the E2, E3, and E4 isoforms) and age-related macular degeneration (AMD), and the mechanism underlying the association. Genomic DNA was extracted from 133 clinically screened controls, 94 volunteers with a younger mean age, 120 patients with advanced AMD, and 40 archived ocular AMD slides for single nucleotide polymorphism typing. The effects of recombinant ApoE isoforms on CCL2 (a chemokine), CX3CR1 (a chemokine receptor), and VEGF (a cytokine) expression in cultured human retinal pigment epithelium (RPE) cells were tested and serum cholesterol profiles of the clinically screened subjects were analyzed. ApoE112R (E4) distribution differed significantly between AMD patients and controls. ApoE112R allele frequency was 10.9% in the AMD group when compared with 16.5% in the younger controls and 18.8% in the clinically screened controls. The pathologically diagnosed archived AMD cases had the lowest allele frequency of 5%. No significant differences in ApoE158C (E2) distribution were observed among the groups. A meta-analysis of 8 cohorts including 4,289 subjects showed a strong association between AMD and 112R, but not 158C. In vitro studies found that recombinant ApoE suppresses CCL2 and VEGF expression in RPE cells. However, the E4 isoform showed more suppression than E3 in both cases. These results further confirm the association between ApoE112R and a decreased risk of AMD development. The underlying mechanisms may involve differential regulation of both CCL2 and VEGF by the ApoE isoforms.

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“…APOE is often found to modify the effects of exposure on neurodegenerative processes [Haan, Shemanski, et al 1999 ]. Recent work in a variety of populations shows that the Apolipoprotein APOE4 allele, a major risk factor for dementia, Alzheimer's and vascular dementia, may modify CRP such that it is lower among carriers of the '4' allele than in non carriers [Judson, Brain, et al 2004] [van Oijen, de Maat, et al 2006] [Chasman, Kozlowski, et al 2006] [Eiriksdottir, Aspelund, et al 2006] [Marz, Scharnagl, et al 2004] [Rontu, Ojala, et al 2006]. Although this suggests that the influence of CRP on dementia rate could vary by APOE4 status, none of the studies of CRP and dementia or cognitive impairment have addressed potential modification of the association between CRP and dementia by APOE4.…”

Section: Introductionmentioning

confidence: 99%

C-reactive protein and rate of dementia in carriers and non carriers of Apolipoprotein APOE4 genotype

Haan

Aiello

West

et al. 2008

Neurobiology of Aging

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Background-Those with an apolipoprotein APOE4 allele (APOE4) have lower C-reactive protein (CRP) than those without APOE4. Whether APOE4 modifies the effects of CRP on rate of all cause dementia, cognitive impairment or Alzheimer's disease (AD) is not established.Methods-All cause dementia and cognitive impairment without dementia (CIND) was determined over five follow up visits from 1998-2006 in an ongoing cohort of older Latinos. The association between high sensitivity CRP and dementia/CIND, all cause dementia and Alzheimer's disease by APOE4 status was examined in semi-parametric survival models with covariate adjustments.Results-CRP was significantly lower among those with APOE4 than in those without. Among those with APOE4, CRP was associated with lower rates of combined dementia/CIND (HR: 0.60, 95% CL: 0.20-0.91, p=0.03) from a fully adjusted model. Among those with no APOE4, there was no effect of CRP on dementia/CIND rates (HR: 0.94, 95% CL:0.67-1.33).Conclusions-Lower CRP in those with APOE4 may reflect immune effects of the APOE4 genotype. Higher CRP in those with APOE4 may be a marker of better immune function, leading to lower rate of dementia and AD.

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New and confirmatory evidence of an association between APOE genotype and baseline C-reactive protein in dyslipidemic individuals

Cited by 58 publications

References 34 publications

Heritability of serum hs-CRP concentration and 5-year changes in the Stanislas family study: association with apolipoprotein E alleles

Heritability of serum hs-CRP concentration and 5-year changes in the Stanislas family study: association with apolipoprotein E alleles

An apolipoprotein E variant may protect against age‐related macular degeneration through cytokine regulation

C-reactive protein and rate of dementia in carriers and non carriers of Apolipoprotein APOE4 genotype

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