APOE distribution in world populations with new data from India and the UK

Singh, Parjit S.; Singh, Monica; Mastana, Sarabjit S.

doi:10.1080/03014460600594513

Cited by 290 publications

(284 citation statements)

References 184 publications

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“…5-1% are e2/e2. In Europe there is a geographic cline, with 2-fold higher prevalence of the e4 allele in northern Europe compared with southern Europe (Corbo & Scacchi, 1999;Eichner et al 2002;Singh et al 2006 ; Table 3), which is likely to make a contribution to the north-south differences in CVD incidence observed.…”

Section: Apoe Allelic Frequency and Genotype Distributionsmentioning

confidence: 99%

ApoE genotype, cardiovascular risk and responsiveness to dietary fat manipulation

et al. 2007

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Cardiovascular risk is determined by the complex interactions between genetic and environmental factors. The apoE genotype represents the most-widely-studied single nucleotide polymorphism in relation to CVD risk, with > 3600 publications cited in PubMed. Although originally described as a mediator of lipoprotein metabolism, the lipoprotein-independent functions of apoE are being increasingly recognised, with limited data available on the potential impact of genotype on these metabolic processes. Furthermore, although meta-analyses suggest that apoE4 carriers may have a 40-50% increased CVD risk, the associations reported in individual studies are highly heterogeneous and it is recognised that environmental factors such as smoking status and dietary fat composition influence genotype-phenotype associations. However, information is often derived from observational studies or small intervention trials in which retrospective genotyping of the cohort results in small group sizes in the rarer E2 and E4 subgroups. Either larger well-standardised intervention trials or smaller trials with prospective recruitment according to apoE genotype are needed to fully establish the impact of diet on genotype-CVD associations and to establish the potential of dietary strategies such as reduced total fat, saturated fat, or increased antioxidant intakes to counteract the increased CVD burden in apoE4 carriers. ApoE genotype: CVD: Dietary fat: Oxidative status: InflammationThe impact of single nucleotide polymorphisms on risk of chronic diseases such as CVD, and the ability of dietary factors to manipulate genotype-phenotype associations, is being increasingly recognised. Undoubtedly, the mostwidely-studied gene variant in relation to CVD is the apoE e (e2, e3, e4) genotype. Since its discovery in 1973 the central role of the apoE protein in lipoprotein metabolism has been comprehensively investigated and reported. The 40-50 % higher risk of CVD in apoE4 carriers (Song et al. 2004) has been traditionally attributed to moderately higher circulating cholesterol and TAG levels. However, it is becoming increasingly recognised that an effect on lipoprotein metabolism alone cannot explain the disease differential and that the impact of an apoE4 genotype is largely lipoprotein independent. Roles of macrophagederived apoE protein on vascular health and atherogenesis are being identified, with apoE thought to impact on oxidative status and in an autocrine and paracrine manner affect macrophage, vascular smooth muscle cell, endothelial cell and platelet function. An impact of genotype on these localised functions of apoE could in part explain the impact of genotype on CVD pathology, as will be discussed.Additionally, apoE genotype has been shown to affect the responsiveness to the total fat content and fatty acid composition of the diet. Manipulation of dietary fat content may serve as a means of reducing the increased CVD burden associated with an apoE4 genotype.

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Section: Apoe Allelic Frequency and Genotype Distributionsmentioning

confidence: 99%

ApoE genotype, cardiovascular risk and responsiveness to dietary fat manipulation

et al. 2007

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“…10). The e2 allele is rare or absent in Inuits, South Americans, Siberians and Mongolians, but relatively frequent in sub-Saharans, Malaysian and Papuans (10) . At the continental level, allele frequencies of apoE e3 and e4 are inversely correlated in Europe, Africa and North America.…”

Section: Geographic Distribution Of Apoe Genotypesmentioning

confidence: 99%

“…968 in Indians and 0 . 356 in Papuans (10) . Highest apoE e4 frequencies are found in Central Africa (including Pygmies (0 .…”

Section: Geographic Distribution Of Apoe Genotypesmentioning

confidence: 99%

“…407) (9) and Tutsi (0 . 385) (10) ); Oceania (including Papuans (0 . 368) and Australian Aborigines (0 .…”

Section: Geographic Distribution Of Apoe Genotypesmentioning

confidence: 99%

“…Correlation of (a) apoE e4, (b) apoE e3 and (c) apoE e2 allele frequencies in Europe with respective latitudes. Data on allele frequency and latitude were adapted from Singh et al (10) and Rodrigues et al (13) . Linear regression of apoE allele frequency and latitude was calculated applying Pearson's correlation analysis and is given as regression coefficient R with corresponding P-values.…”

Section: Geographic Distribution Of Apoe Genotypesmentioning

confidence: 99%

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ApoE genotype: from geographic distribution to function and responsiveness to dietary factors

2012

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ApoE is a key protein in lipid metabolism with three major isoforms. ApoE allele frequencies show non-random global distribution especially in Europe with high apoE e3 frequency in the Mediterranean area, whereas the apoE e4 genotype is enriched in Northern Europe. The apoE e4 genotype is one of the most important genetic risk factors for age-dependent chronic diseases, including CVD and Alzheimer's disease (AD). The apoE polymorphism has been shown to impact on blood lipids, biomarkers of oxidative stress and chronic inflammation, which all may contribute to the isoform-dependent disease risk. Studies in mice and human subjects indicate that the apoE e3 but not the apoE e4 genotype may significantly benefit from dietary flavonoids (e.g. quercetin) and n-3 fatty acids. Metabolism of lipid soluble vitamins E and D is likewise differentially affected by the apoE genotype. Epidemiological and experimental evidence suggest a better vitamin D status in apoE e4 than e3 subjects indicating a certain advantage of e4 over e3. The present review aims at evaluation of current data available on interactions between apoE polymorphism and dietary responsiveness to flavonoids, fat soluble vitamins and n-3 fatty acids. Likewise, distinct geographic distribution and chronic disease risk of the different apoE isoforms are addressed.

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Polygenic risk score penetrance & recurrence risk in familial Alzheimer disease

Qiao

Lee

Reyes‐Dumeyer

et al. 2023

Ann Clin Transl Neurol

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Objective: To compute penetrance and recurrence risk using a genome-wide PRS (including and excluding the APOE region) in families with Alzheimer's disease. Methods: Genotypes from the National Institute on Aging Late-Onset Alzheimer's Disease Family-Based Study and a study of familial Alzheimer's disease in Caribbean Hispanics were used to compute PRS with and without variants in the 2 MB region flanking APOE. PRS was calculated in using clumping/ thresholding and Bayesian methods and was assessed for association with Alzheimer's disease and age at onset. Penetrance and recurrence risk for carriers in highest and lowest PRS quintiles were compared separately within APOE-e4 carriers and non-carriers. Results: PRS excluding the APOE region was strongly associated with clinical and neuropathological diagnosis of AD. PRS association with AD was similar in participants who did not carry an APOE-e4 allele (OR = 1.74 [1.53-1.91]) compared with APOE-e4 carriers (1.53 [1.4-1.68]). Compared to the lowest quintile, the highest PRS quintile had a 10% higher penetrance at age 70 (p = 0.0006) and a 20% higher penetrance at age 80 (p < 10e-05). Stratifying by APOE-e4 allele, PRS in the highest quintile was significantly more penetrant than the lowest quintile, both, within APOE-e4 carriers (14.5% higher at age 80, p = 0.002) and non-carriers (26% higher at 80, p < 10e-05). Recurrence risk for siblings conferred by a co-sibling in the highest PRS quintile increased from 4% between the ages of 65-74 years to 39% at age 85 and older. Interpretation: PRS can be used to estimate penetrance and recurrence risk in familial Alzheimer's disease among carriers and non-carries of APOE-e4.

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APOE distribution in world populations with new data from India and the UK

Cited by 290 publications

References 184 publications

ApoE genotype, cardiovascular risk and responsiveness to dietary fat manipulation

ApoE genotype, cardiovascular risk and responsiveness to dietary fat manipulation

ApoE genotype: from geographic distribution to function and responsiveness to dietary factors

Polygenic risk score penetrance & recurrence risk in familial Alzheimer disease

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