Association of APOE gene polymorphism with lipid profile and coronary artery disease in Afro-Caribbeans

Larifla, Laurent; Armand, C.; Bangou, J.; Blanchet-Deverly, Anne; Numeric, P.; Fonteau, Christiane; Michel, Carl-Thony; Ferdinand, Séverine; Bourrhis, Véronique; Vélayoudom-Céphise, Fritz-Line

doi:10.1371/journal.pone.0181620

Cited by 32 publications

(39 citation statements)

References 35 publications

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“…After taking the environmental factors into consideration, patients with CT or TT genotypes ( CT : adjusted OR 1.44, 95% CI 1.27–3.67; TT : adjusted OR 1.56, 95% CI 0.88–2.78) had a higher risk for CAD. Above all, these results indicate that genotypes CT and TT and allele T of MTHFR C677T were independent risk factors for the onset of CAD, consistent with previous studies [17-19]. In addition, our results showed that genotype TT at MTHFR C677T was associated with more severe coronary lesions.…”

Section: Discussionsupporting

confidence: 93%

A Case-Control Study of the Association of the Polymorphisms of MTHFR and APOE with Risk Factors and the Severity of Coronary Artery Disease

et al. 2019

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Objectives: To explore the association between single-nucleotide polymorphisms (SNPs) in MTHFR and APOE and the risk of CAD and, more importantly, the severity of CAD and the profile of serum lipids, we performed a case-control study in a Chinese Han population. Methods: A total of 1,207 cases of consecutive CAD-suspected inpatients were recruited, and 406 CAD cases and 231 non-CAD controls were enrolled for the final analysis after screening for exclusion criteria. All subjects had undergone coronary angiography, and the severity of CAD was evaluated by 2 cardiologists according to the Gensini scores. The genotypes of MTHFR and APOEwere detected using real-time PCR, and then verified by Sanger sequencing. Environmental risk factors, such as age, sex, smoking, alcohol consumption, hypertension, diabetes, dyslipidemia, and BMI were collected. Statistical analyses (the χ² test, binary logistic regression analysis, and ordinal polytomous logistic regression analysis) were performed with SPSS v16.0. Results: The genotypes ofall the subjects included in the CAD and non-CAD groups in this study were successfully detected, with an agreement of 100% with Sanger sequencing. The distributions of genotypes CT and TT at MTHFR C667T were higher in CAD cases than in non-CAD controls (OR 1.99, 95% CI 1.34–2.95; OR 1.77, 95% CI 1.18–2.67; p < 0.05), whereas genotype AC at MTHFR A1298Cwas lower in CAD cases (OR 0.71, 95% CI 0.50–1.02; p < 0.05). A significant association was observed in genotypes CT and TT at MTHFR C667T and the risk of CAD (OR 1.44, 95% CI 1.27–3.67; OR 1.56, 95% CI 0.88–2.78; p < 0.05). Both genotypes and alleles of APOE were comparable in the CAD cases and non-CAD controls (p > 0.05). The genotype TT at MTHFR C667T and ε4+ at APOE were more likely to be found in the CAD subgroup with a Gensini score ≥72 (p = 0.040 and p = 0.028, respectively). Meanwhile, in the patients with genotype TT,a higher level of serum Hcy was detected, while genotype ε4+ patients possessed higher levels of serum apolipoprotein E (ApoE) and low-density lipoprotein cholesterol (LDL-C) than other genotypes. Conclusion: This study revealed that the SNP site of MTHFR C667Tis associatedwith the risk of CAD in this Chinese Han population. In addition, the genotypes of TT in MTHFR C667T and ε4+in APOE may increase the severity of CAD, and higher Hcy, LDL-C, and ApoE levels may be involved in this pathogenic process.

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Section: Discussionsupporting

confidence: 93%

A Case-Control Study of the Association of the Polymorphisms of MTHFR and APOE with Risk Factors and the Severity of Coronary Artery Disease

et al. 2019

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“…An early illustration of AD risk differences based on APOE genotype and ethnicity is shown in Figure 5B (Farrer et al, 1997). Similarly, APOE alleles appear to have no effect on lobar hemorrhage in African-Americans (Sawyer et al, 2018) or on CAD in Afro-Carribeans (Larifla et al, 2017). Recent efforts further demonstrate that the continuum of African ancestry in admixed African-Americans impacts the effect of APOE4 on AD and cognitive decline (Deters et al, 2018;Rajabli et al, 2018), such that APOE4 confers greater risk with decreasing percent of African ancestry.…”

Section: Apoe and Ancestral Backgroundmentioning

confidence: 99%

A Quarter Century of APOE and Alzheimer’s Disease: Progress to Date and the Path Forward

Belloy

Napolioni

Greicius

2019

Neuron

358

340

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Alzheimer's disease (AD) is considered a polygenic disorder. This view is clouded, however, by lingering uncertainty over how to treat the quasi ''monogenic'' role of apolipoprotein E (APOE). The APOE4 allele is not only the strongest genetic risk factor for AD, it also affects risk for cardiovascular disease, stroke, and other neurodegenerative disorders. This review, based mostly on data from human studies, ranges across a variety of APOE-related pathologies, touching on evolutionary genetics and risk mitigation by ethnicity and sex. The authors also address one of the most fundamental question pertaining to APOE4 and AD: does APOE4 increase AD risk via a loss or gain of function? The answer will be of the utmost importance in guiding future research in AD. (A) The three main APOE isoforms APOE2, APOE3, and APOE4, respectively, encoded by the Apolipoprotein E2, E3, and E4 alleles, are the result of non-synonymous polymorphisms that cause amino acid changes at position 112 and 158 of the APOE protein (Rall et al., 1982; Weisgraber et al., 1981). APOE3 is the most common variant in the general population. The APOE4 variant is a major genetic risk factor for AD, while APOE2 is protective (Farrer et al., 1997). (B) Structural models of lipid-free APOE are shown for each major isoform, based on X-ray crystallography, structure prediction, and circular dichroism spectroscopy (Zhong and Weisgraber, 2009). The N-terminal domain contains APOE's low-density lipoprotein receptor (LDLR) region at amino acid residues 134-150, while the C-terminal holds the lipid-binding region at residues 244-272. Amino acid substitutions in APOE4 promote a salt bridge between Arg61 and Glu255, which, compared to the APOE2 and APOE3 variants, drives increased domain interaction between the N-and C-terminal domains. In (A), APOE allele frequencies are obtained, with permission, from American

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“…More recently, several studies have investigated the relationships between APOE polymorphisms and cardiovascular and cerebrovascular disease [16][17][18]. However, the identified associations between APOE polymorphisms and CAD were highly inconsistent [19]. Furthermore, no information has been published regarding the relationship between APOE polymorphism and the risk of CAD in the Hakka ethnic group in China.…”

Section: Introductionmentioning

confidence: 99%

Association between apolipoprotein E gene polymorphism and the risk of coronary artery disease in Hakka postmenopausal women in southern China

et al. 2020

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Background: Apolipoprotein E (APOE) is involved in the pathogenesis of atherosclerosis and conveys a higher risk of coronary artery disease (CAD). The aim of the present study was to investigate the possible association between APOE gene polymorphism and the risk of CAD in postmenopausal Hakka women in southern China. Methods: The APOE genotypes of 653 CAD patients and 646 control participants were determined by the polymerase chain reaction (PCR) and hybridization to a Sinochip. Results: The prevalence of each APOE genotype differed between CAD patients and control participants (P = 0.011). The E3/E3 genotype was the most common and the E2/E2 genotype was the least common in the study sample. Moreover, the presence of ε4 allele was associated with higher serum concentrations of triglycerides (TG), total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C), and lower concentration of high-density lipoprotein-cholesterol (HDL-C). Multiple logistic regression analysis revealed that participants with ε4 allele have a significantly higher risk of CAD after adjustment for the presence of diabetes mellitus and hypertension, and their serum uric acid, TC, and LDL-C concentrations (adjusted odds ratio (OR) 1.50, 95% confidence interval (CI) 1.10-2.05, P = 0.010). Conclusions: The present results suggest that APOE polymorphism is associated with a higher risk of CAD in postmenopausal Hakka women in southern China.

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Association of APOE gene polymorphism with lipid profile and coronary artery disease in Afro-Caribbeans

Cited by 32 publications

References 35 publications

A Case-Control Study of the Association of the Polymorphisms of <b><i>MTHFR</i></b> and <b><i>APOE</i></b> with Risk Factors and the Severity of Coronary Artery Disease

A Case-Control Study of the Association of the Polymorphisms of <b><i>MTHFR</i></b> and <b><i>APOE</i></b> with Risk Factors and the Severity of Coronary Artery Disease

A Quarter Century of APOE and Alzheimer’s Disease: Progress to Date and the Path Forward

Association between apolipoprotein E gene polymorphism and the risk of coronary artery disease in Hakka postmenopausal women in southern China

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