ApoE phenotype is associated with inflammatory markers in middle-aged subjects

Ukkola, Olavi; Kunnari, Anne; Jokela, Maarit; Pãivänsalo, M.; Kesäniemi, Y. Antero

doi:10.1007/s00011-008-8215-2

Cited by 8 publications

(8 citation statements)

References 37 publications

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“…Our results that E3E4 and E4E4 genotype are associated with lower CRP levels are in agreement with previous studies ( 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ). In a few studies, there was no association between APOE E4 allele and low CRP levels ( 30 , 31 ).…”

Section: Discussionsupporting

confidence: 94%

“…Since Manttari and colleagues first described the association of APOE E4 allele with low CRP levels in 2001, many studies have investigated relationships between APOE genotype and CRP levels. Most studies have reported that E4 allele is associated with low levels of CRP ( 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ). However, there is little research on the relationship between other markers of inflammation and APOE genotype.…”

Section: Introductionmentioning

confidence: 99%

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APOEPolymorphism Is Associated with C-reactive Protein Levels but Not with White Blood Cell Count: Dong-gu Study and Namwon Study

et al. 2015

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We evaluated the association of the APOE polymorphism with serum C-reactive protein levels and white blood cell count in two large population-based studies in Korean. The datasets included the Dong-gu study (n = 8,893) and the Namwon Study (n = 10,032). APOE genotypes were identified by polymerase chain reaction-restriction fragment length polymorphism. Multivariable linear regression analysis was performed to evaluate the relationship of APOE genotypes with C-reactive protein levels and white blood cell count with adjustments for age, sex, body mass index, smoking, diabetes, hypertension, and serum lipids. In the multivariate model, carriers of E3E4 or E4E4 genotype had significantly lower C-reactive protein levels compared with carriers of E3E3 genotype group (0.50 mg/L vs. 0.67 mg/L; 0.37 mg/L vs. 0.67 mg/L, respectively, for the Dong-gu Study and 0.47 mg/L vs. 0.66 mg/L; 0.45 mg/L vs. 0.66 mg/L, respectively, for the Namwon Study). However, there was no difference in white blood cell count among APOE genotypes. We found that the APOE E4 allele is associated with lower C-reactive protein levels, but not white blood cell count. Our results suggest that APOE genotype may influence C-reactive protein levels through non-inflammatory pathway.Graphical Abstract

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Section: Discussionsupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

APOEPolymorphism Is Associated with C-reactive Protein Levels but Not with White Blood Cell Count: Dong-gu Study and Namwon Study

et al. 2015

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“…Relative to APOEε2 and APOEε3 carriers, APOEε4 carriers generate less ApoE protein in periphery and brain ( Larson et al, 2000 ). Given the reduced amounts of ApoE protein in APOEε4 carriers, this population could be predisposed to a heightened inflammatory response when encountering a sterile inducer or infection ( Ukkola et al, 2009 ; Gale et al, 2014 ; Tai et al, 2015 ).…”

Section: Apoeε4 Inflammation and Alzheimer’s Diseasementioning

confidence: 99%

“…Surprisingly, however, this is not the case, at least with CRP. Studies have consistently shown that CRP levels are lower in APOEε4 carriers ( Ukkola et al, 2009 ; Lima et al, 2014 ; Metti et al, 2014 ; Yun et al, 2015 ). Marz et al (2004) proposed that the metabolism of CRP might be associated with the mevalonate/cholesterol synthetic pathway, which might be downregulated in APOEε4 carriers.…”

Section: Apoeε4 Inflammation and Alzheimer’s Diseasementioning

confidence: 99%

Inflammation: Bridging Age, Menopause and APOEε4 Genotype to Alzheimer’s Disease

Mishra

Brinton

2018

Front. Aging Neurosci.

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Neuro-inflammatory processes that contribute to development of Alzheimer’s are evident early in the latent prodromal phase and worsen during the course of the disease. Despite substantial mechanistic and clinical evidence of inflammation, therapeutic approaches targeting inflammation have failed to alter the course of the disease. Disparate results from epidemiological and clinical trials targeting inflammation, highlight the complexity of the inflammatory process. Herein we review the dynamics of the inflammatory process across aging, midlife endocrine transitions, and the APOEε4 genotype and their contribution to progression of Alzheimer’s disease (AD). We discuss the chronic inflammatory processes that are activated during midlife chronological and endocrine aging, which ultimately limit the clearance capacity of microglia and lead to immune senescence. Aging, menopause, and APOEε4 combine the three hits of a compromised bioenergetic system of menopause with the chronic low grade innate inflammation of aging with the APOEε4 dyslipidemia and adaptive immune response. The inflammatory immune response is the unifying factor that bridges across each of the risk factors for AD. Immune system regulators that are specific to stage of disease and inflammatory phenotype would provide a therapeutic strategy to disconnect the bridge that drives disease. Outcomes of this analysis provide plausible mechanisms underlying failed clinical trials of anti-inflammatory agents in Alzheimer’s patients. Further, they highlight the need for stratifying AD clinical trial cohorts based on inflammatory phenotype. Combination therapies that include targeted use of anti-inflammatory agent’s specific to the immune phenotype are considered.

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“…Eighteen studies 12,13,[15][16][17][18][19][20][21][22][26][27][28][29][30][31][32]34 were included into the study of e4 versus e3 (including 29 comparisons). Seventeen studies 12,13,[15][16][17][18][19][20][21][22][26][27][28][29][30][31][32] were included into the study of e2 versus e4 (including 27 comparisons).…”

Section: Study Characteristics For the Relationship Between Apoe Genementioning

confidence: 99%

Relationship between apolipoprotein E gene polymorphism with triglyceride level in patients with renal diseases

et al. 2013

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Apolipoprotein E (apoE), one of the major plasma lipoproteins, plays a major role in the transport and metabolism of lipids by acting as a ligand. apoE gene contains three potential alleles: e2, e3 and e4, forming six genotypes: E2E2, E2E3, E2E4, E3E3, E3E3 and E4E4. Association between apoE gene polymorphism and triglyceride (TG) is still controversial. There was no any meta-analysis to explore the association of apoE gene polymorphism with triglyceride level, and this meta-analysis was performed to evaluate the association between apoE gene polymorphism and triglyceride in patients with renal diseases. A predefined literature search and selection of eligible relevant studies were performed to collect data from electronic databases. Twenty-four articles were identified for the analysis of association between apoE gene polymorphism and triglyceride level. Subjects with E2E3 or E3E4 had a higher TG than those with E3E3. Subjects with e4 had a higher TG than those with e3. Subjects with e2 had a slightly higher TG than those with e3, although there was no statistical difference. Interestingly, subjects with e4 had a much higher TG than those with e2. In conclusion, E2E3, E3E4 or e4 was associated with higher level of TG. However, more studies should be performed in the future.

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ApoE phenotype is associated with inflammatory markers in middle-aged subjects

Abstract: ApoE phenotype is an independent determinant of plasma resistin and hsCRP levels. The extent of atherosclerosis and renal function seem to modify the effects of apoE phenotype on inflammatory parameters.

Cited by 8 publications

References 37 publications

APOEPolymorphism Is Associated with C-reactive Protein Levels but Not with White Blood Cell Count: Dong-gu Study and Namwon Study

APOEPolymorphism Is Associated with C-reactive Protein Levels but Not with White Blood Cell Count: Dong-gu Study and Namwon Study

Inflammation: Bridging Age, Menopause and APOEε4 Genotype to Alzheimer’s Disease

Relationship between apolipoprotein E gene polymorphism with triglyceride level in patients with renal diseases

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