载脂蛋白 E 基因变异在儿科发病多发性硬化中的意义：在希腊队列中，可能与疾病易感性及其临床特征相关。

Implication of Apolipoprotein E gene variants in pediatric-onset multiple sclerosis: Possible association with disease susceptibility and its clinical characteristics, in a Hellenic cohort.

机构信息

Research Immunogenetics Laboratory, First Department of Neurology, School of Medicine, National and Kapodistrian University of Athens, Aeginition University Hospital, Vas. Sofias 72-74, 11528, Athens, Greece.

Neurology Department, Medical School, University of Cyprus, Nicosia 1678, Cyprus.

出版信息

Mult Scler Relat Disord. 2024 Oct;90:105797. doi: 10.1016/j.msard.2024.105797. Epub 2024 Aug 8.

DOI:10.1016/j.msard.2024.105797

PMID:39146895

Abstract

BACKGROUND

Apolipoprotein E (ApoE) plays a major role in lipid homeostasis and myelination in the central nervous system. Although ApoE gene variants have been linked with cognitive impairment in the setting of Multiple sclerosis (MS), no association with disease susceptibility was found, while similar studies in pediatric-onset MS (POMS) are limited.

OBJECTIVE

This study aims to explore the role of ApoE gene variants in the POMS susceptibility of a Hellenic cohort and any association with disease features.

METHODS

112 POMS, fulfilling the revised IPMSSG 2013 criteria, 391 adult-onset MS (AOMS) and 200 healthy controls (HCs), were enrolled. After DNA extraction, ApoE genotyping was performed by a polymerase chain reaction and sequence-specific-oligonucleotide technique.

RESULTS

ApoE2/E3 genotype and ApoE2 allele were found to be significantly more frequent among POMS patients compared to HCs [(20.5% vs 11 %, OR [95 %]: 2.1 (1.1-4.0), p = 0.03)], and [(11% vs 5.3 %, OR [95 %]: 2.3 (1.2-4.1), p = 0.01)], respectively. Additionally, significantly lower frequencies of the ApoE3/E3 genotype and the ApoE3 allele were observed in POMS patients compared to HCs (59.8% vs 79 %, OR [95 %]:0.40 (0.24-0.65), p = 0.0005 and 79% vs 89 % 0.46, OR [95 %]: (0.30-0.73), p = 0.001)], respectively.

CONCLUSIONS

The ApoE2 allele may represent a novel risk factor for POMS development.

摘要

背景

载脂蛋白 E（ApoE）在中枢神经系统的脂质平衡和髓鞘形成中起主要作用。尽管 ApoE 基因变异与多发性硬化症（MS）患者的认知障碍有关，但未发现与疾病易感性有关，而儿科发病的多发性硬化症（POMS）的类似研究有限。

目的

本研究旨在探讨 ApoE 基因变异在希腊队列 POMS 易感性中的作用及其与疾病特征的任何关联。

方法

纳入了 112 名符合修订后的 IPMSSG 2013 标准的 POMS 患者、391 名成人发病 MS（AOMS）患者和 200 名健康对照者（HCs）。提取 DNA 后，通过聚合酶链反应和序列特异性寡核苷酸技术进行 ApoE 基因分型。

结果

与 HCs 相比，POMS 患者中 ApoE2/E3 基因型和 ApoE2 等位基因的频率明显更高[（20.5% vs 11%，OR[95%]：2.1（1.1-4.0），p=0.03]）和[（11% vs 5.3%，OR[95%]：2.3（1.2-4.1），p=0.01）]。此外，与 HCs 相比，POMS 患者中 ApoE3/E3 基因型和 ApoE3 等位基因的频率明显更低[（59.8% vs 79%，OR[95%]：0.40（0.24-0.65），p=0.0005）和 79% vs 89%，OR[95%]：0.46（0.30-0.73），p=0.001）]。