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基因内的一种多态性与多发性硬化症男性患者更高的复发数量有关。

A Polymorphism Within the Gene Is Associated With a Higher Relapse Number in Male Patients of Multiple Sclerosis.

机构信息

Laboratorio de Investigación en Genética de Enfermedades Complejas, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Red Española de Esclerosis Múltiple (REEM), Madrid, Spain.

Grupo de Investigación de Factores Ambientales en Enfermedades Degenerativas, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Red Española de Esclerosis Múltiple (REEM), Madrid, Spain.

出版信息

Front Immunol. 2020 May 5;11:771. doi: 10.3389/fimmu.2020.00771. eCollection 2020.

Abstract

Myelin basic protein (MBP) is thought to be one of the key autoantigens in multiple sclerosis (MS) development. A recent study described the association of the single nucleotide polymorphism (SNP) rs12959006, within the gene, with a higher risk of relapse and worse prognosis. We aim at studying potential associations of this SNP to MS in an independent population. Clinical data of the first 5 years of the disease were collected retrospectively from 291 MS confirmed patients. polymorphism rs12959006 was genotyped in all patients. Associations with EDSS, number of relapses and serology for Herpesvirus 6 (HHV-6) and Epstein Barr (EBV) viruses were studied. Lymphocyte activation measured by CD69 expression was also analyzed according to sex and rs12959006 genotype. The rs12959006 polymorphism contributed significantly to a higher number of relapses at 5 years after onset only in male patients (rs12959006TT β = 0.74 [0.36-1.09]; = 7 × 10). Titers of anti-HHV6 IgG antibodies showed also a mild association with relapses, both in male and female patients (β = 0.01 [0.01-0.02]; = 3.7 × 10). Both the genetic variation in and HHV-6 infection aid in predicting a higher number of relapses during the first years of MS. The association described in rs12959006T is exclusive to male patients.

摘要

髓鞘碱性蛋白(MBP)被认为是多发性硬化症(MS)发展过程中的关键自身抗原之一。最近的一项研究描述了 基因内的单核苷酸多态性(SNP)rs12959006 与复发风险增加和预后较差之间的关联。我们旨在研究该 SNP 与独立人群中 MS 的潜在关联。从 291 例确诊的 MS 患者中回顾性收集了疾病前 5 年的临床数据。对所有患者进行了 rs12959006 多态性基因分型。研究了与 EDSS、复发次数以及疱疹病毒 6(HHV-6)和 Epstein-Barr(EBV)病毒的血清学之间的关联。还根据性别和 rs12959006 基因型分析了通过 CD69 表达测量的淋巴细胞激活情况。rs12959006 多态性仅在男性患者中在发病后 5 年内显著导致复发次数增加(rs12959006TT β=0.74 [0.36-1.09]; = 7×10)。抗 HHV-6 IgG 抗体的滴度也与男性和女性患者的复发均有轻度关联(β=0.01 [0.01-0.02]; = 3.7×10)。 中的遗传变异和 HHV-6 感染均有助于预测 MS 发病初期的复发次数增加。在 rs12959006T 中描述的关联仅发生在男性患者中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5e/7214696/14ee2719c9b3/fimmu-11-00771-g001.jpg

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