与中国复发缓解型多发性硬化症患者风险增加相关的变异体。

Variant of Associated with Increasing Risk in Chinese Patients with Relapsing-remitting Multiple Sclerosis.

机构信息

Department of Neurology, Huashan Hospital, Fudan University, Shanghai 200040, China.

Department of Neurology and Research Center of Neurology, Second Affiliated Hospital, Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang, China.

出版信息

Chin Med J (Engl). 2018 Mar 20;131(6):643-647. doi: 10.4103/0366-6999.226892.

DOI:10.4103/0366-6999.226892

PMID:29521285

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5865308/

Abstract

BACKGROUND

Multiple sclerosis (MS) is a common central nervous system autoimmune disorder. Increasing number of genome-wide association study (GWAS) analyses hint that MS is strongly associated with genetics. Unfortunately, almost all the GWAS analyses were Caucasian population based. Numbers of risk loci might not be replicated in Chinese MS patients. Hence, we performed a MassArray Assay to genotype the previously reported variants located in the transcription regulation genes in order to elucidate their role in the Chinese MS patients.

METHODS

One hundred and forty-two relapsing-remitting MS (RRMS) patients and 301 healthy controls were consecutively collected from September 2, 2008, to June 7, 2013, as stage 1 subjects. Eight reported transcription regulation-related single-nucleotide polymorphisms (SNPs) were genotyped using the Sequenom MassArray system. In stage 2, another 44 RRMS patients and 200 healthy controls were consecutively collected and Sanger sequenced from April 7, 2015, to June 29, 2017, for the validation of positive results in stage 1. Differences in allele and genotype frequencies between patients and healthy controls, odds ratios, and 95% confidence intervals were calculated with the Chi-square test or Fisher's exact test. Hardy-Weinberg equilibrium was tested also using the Chi-square test.

RESULTS

In stage 1 analysis, we confirmed only one previously reported risk variant, rs11129295 in EOMES gene. We found that the frequency of T/T genotype was much higher in MS group (χ = 10.251, P = 0.005) and the T allele of rs11129295 increased the risk of MS (χ = 10.022, P = 0.002). In stage 2 and combined analyses, the T allele of rs11129295 still increased the risk of MS (χ = 4.586, P = 0.030 and χ = 16.378, P = 5.19 × 10, respectively).

CONCLUSIONS

This study enhances the knowledge that the variant of EOMES is associated with increasing risk in Chinese RRMS patients and provides a potential therapeutic target in RRMS.

摘要

背景

多发性硬化症（MS）是一种常见的中枢神经系统自身免疫性疾病。越来越多的全基因组关联研究（GWAS）分析表明，MS 与遗传密切相关。不幸的是，几乎所有的 GWAS 分析都是基于白种人人群。风险基因座的数量可能无法在中国人 MS 患者中复制。因此，我们进行了 MassArray 分析，以对位于转录调控基因中的先前报道的变体进行基因分型，以阐明其在中国人 MS 患者中的作用。

方法

从 2008 年 9 月 2 日至 2013 年 6 月 7 日，连续收集 142 例复发缓解型 MS（RRMS）患者和 301 名健康对照者作为第 1 阶段的研究对象。使用 Sequenom MassArray 系统对 8 个已报道的转录调控相关单核苷酸多态性（SNP）进行基因分型。在第 2 阶段，从 2015 年 4 月 7 日至 2017 年 6 月 29 日，连续收集并对另外 44 例 RRMS 患者和 200 名健康对照者进行 Sanger 测序，以验证第 1 阶段的阳性结果。采用卡方检验或 Fisher 精确检验计算患者和健康对照组之间等位基因和基因型频率、优势比和 95%置信区间。采用卡方检验还检验 Hardy-Weinberg 平衡。

结果

在第 1 阶段分析中，我们仅证实了先前报道的风险变异 rs11129295 位于 EOMES 基因。我们发现 MS 组 T/T 基因型的频率明显更高（χ=10.251，P=0.005），rs11129295 的 T 等位基因增加了 MS 的发病风险（χ=10.022，P=0.002）。在第 2 阶段和联合分析中，rs11129295 的 T 等位基因仍增加了 MS 的发病风险（χ=4.586，P=0.030 和 χ=16.378，P=5.19×10-3）。