载脂蛋白 E 基因变异、致动脉粥样硬化指数与非洲人群心血管疾病风险评估：加纳 HIV 和疟疾患者分析。

Apolipoprotein E genetic variation, atherogenic index and cardiovascular disease risk assessment in an African population: An analysis of HIV and malaria patients in Ghana.

机构信息

Department of Medical Biochemistry, Pharmacogenomics and Genomic Medicine Group, School of Medical Sciences, College of Health and Allied Sciences, University of Cape Coast, Cape Coast, Ghana.

Division of Human Genetics, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.

出版信息

PLoS One. 2023 May 3;18(5):e0284697. doi: 10.1371/journal.pone.0284697. eCollection 2023.

DOI:10.1371/journal.pone.0284697

PMID:37134097

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10155972/

Abstract

BACKGROUND

Apolipoprotein E is involved in lipid transport and clearance of lipoprotein through low-density lipoprotein receptors (LDLR). ApoE variation has been linked to cardiovascular disease (CVD) risk. There are 3 isoforms of ApoE which originate from two non-synonymous single nucleotide polymorphisms denoted as ε2, ε3 and ε4. The ε2 isoform is implicated in higher levels of atherogenic lipoprotein with the ε4 isoform causing LDLR downregulation. This leads to variable effects and differential CVD risk. Malaria and HIV are life-threatening diseases affecting several countries globally especially in sub-Saharan Africa. Parasite and viral activities have been implicated in lipid dysregulation leading to dyslipidaemia. This study examined ApoE variation and CVD risk assessment in malaria and HIV patients.

METHODS

We compared 76 malaria-only, 33 malaria-HIV coinfected, 21-HIV-only and 31 controls from a tertiary health facility in Ghana. Fasting venous blood samples were taken for ApoE genotyping and lipid measurements. Clinical and laboratory data were collected with ApoE genotyping performed using Iplex Gold microarray and PCR-RFLP. Cardiovascular disease risk was calculated using the Framingham BMI and cholesterol risk and Qrisk3 tools.

RESULTS

The frequency of C/C genotype for rs429358 was 9.32%, whiles T/T genotype for rs7412 was found in 2.48% of all participants. ε3/ε3 was the most distributed ApoE genotype accounting for 51.55% of the total participants whiles ε2/ε2 was found in 2.48% of participants, with 1 in malaria-only and 3 in HIV-only patients. There was a significant association between ε4+ and high TG (OR = 0.20, CI; 0.05-0.73; p = 0.015), whiles ε2+ was significantly associated with higher BMI (OR; 0.24, CI; 0.06-0.87; p = 0.030) and higher Castelli Risk Index II in females (OR = 11.26, CI; 1.37-92.30; p = 0.024). A higher proportion of malaria-only participants had a moderate to high 10-year CVD risk.

CONCLUSION

Overall malaria patients seem to have a higher CVD risk though the means through which this occurs may be poorly understood. ε2/ε2 genotypes was observed in our population at a lower frequency. Further studies are vital to determine CVD risk in malaria and how this occurs.

摘要

背景

载脂蛋白 E 参与脂蛋白的脂质转运和清除，通过低密度脂蛋白受体（LDLR）。载脂蛋白 E 的变异与心血管疾病（CVD）风险有关。载脂蛋白 E 有 3 种同工型，来源于两个非同义单核苷酸多态性，分别表示为 ε2、ε3 和 ε4。ε2 同工型与致动脉粥样硬化脂蛋白水平升高有关，而 ε4 同工型导致 LDLR 下调。这导致了不同的作用和不同的 CVD 风险。疟疾和艾滋病毒是危及生命的疾病，影响着全球多个国家，特别是撒哈拉以南非洲。寄生虫和病毒的活动与脂质失调有关，导致血脂异常。本研究检测了疟疾和 HIV 患者的载脂蛋白 E 变异和 CVD 风险评估。

方法

我们比较了加纳一家三级医疗机构的 76 名疟疾患者、33 名疟疾-艾滋病毒混合感染患者、21 名艾滋病毒患者和 31 名对照组。抽取空腹静脉血进行载脂蛋白 E 基因分型和血脂检测。收集临床和实验室数据，采用 Iplex Gold 微阵列和 PCR-RFLP 进行载脂蛋白 E 基因分型。使用 Framingham BMI 和胆固醇风险以及 Qrisk3 工具计算心血管疾病风险。

结果

rs429358 的 C/C 基因型频率为 9.32%，而 rs7412 的 T/T 基因型在所有参与者中发现为 2.48%。ε3/ε3 是分布最广的载脂蛋白 E 基因型，占总参与者的 51.55%，而 ε2/ε2 则在 2.48%的参与者中发现，其中 1 例为疟疾患者，3 例为 HIV 患者。ε4+与高甘油三酯（OR = 0.20，CI；0.05-0.73；p = 0.015）之间存在显著相关性，而 ε2+与较高的 BMI（OR；0.24，CI；0.06-0.87；p = 0.030）和女性 Castelli 风险指数 II 较高（OR = 11.26，CI；1.37-92.30；p = 0.024）显著相关。疟疾患者中有较高比例的参与者有中度至高度的 10 年 CVD 风险。