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HLA - DRB1和HLA - DQB1等位基因与斯洛伐克人群的多发性硬化症残疾进展相关。

The HLA-DRB1 and HLA-DQB1 alleles are associated with multiple sclerosis disability progression in Slovak population.

作者信息

Čierny Daniel, Lehotský Ján, Kantorová Ema, Sivák Štefan, Javor Juraj, Kurča Egon, Dobrota Dušan, Michalik Jozef

机构信息

a Jessenius Faculty of Medicine, Department of Clinical Biochemistry , Comenius University in Bratislava and University Hospital Martin , Martin , Slovak Republic.

b Jessenius Faculty of Medicine in Martin, Department of Medical Biochemistry and BioMed , Comenius University in Bratislava , Martin , Slovak Republic.

出版信息

Neurol Res. 2018 Jul;40(7):607-614. doi: 10.1080/01616412.2018.1456711. Epub 2018 Apr 5.

Abstract

OBJECTIVE

The aim of our present study was to analyse the association of HLA-DRB1 and -DQB1 alleles and genotypes with Multiple Sclerosis (MS) disability progression in a cohort of Central European Slovak population.

METHODS

The allele and genotype variants were analyzed in 282 non-related MS patients. Rate of disease disability progression was evaluated using EDSS score in the 5, 7, 10, and 15 year of disease duration, time to reach EDSS score 3 and 5, and MSSS score. Genotyping was performed by polymerase chain reaction with sequence-specific primers.

RESULTS

We found that carriers of homozygous genotype for alleles DRB115 and DQB103 reached EDSS score 3 significantly earlier than non-carriers of these alleles (p = 0.0172; p = 0.00183, respectively). Genotype DQB103/03 carriage was also associated with significantly reduced time to reach EDSS score 5 (p = 0.00316). Lower EDSS score in the 5 year of disease duration was found in carriers of DRB107 allele (p  = 0.028). When MSSS score was used, genotype DRB1*15/15 was found to be less frequent in slow progressing MS patients, when compared to MS patients with mid-rate and rapid disease disability progression (p  = 0.0305).

DISCUSSION

We showed for the first time that HLA-DRB1 and -DQB1 genotypes are genetic markers associated with disability progression in Slovak MS patients. Genotypes DRB115/15 and DQB103/03 were identified as short-term clinical negative prognostic factors, while allele DRB107 carriage appeared to be a positive prognostic marker of better MS outcome.

摘要

目的

我们当前研究的目的是分析中欧斯洛伐克人群队列中HLA - DRB1和 - DQB1等位基因及基因型与多发性硬化症(MS)残疾进展之间的关联。

方法

对282名无亲缘关系的MS患者的等位基因和基因型变异进行分析。使用扩展残疾状态量表(EDSS)评分评估疾病持续5年、7年、10年和15年时的疾病残疾进展率,达到EDSS评分3和5所需的时间,以及多发性硬化症综合评分量表(MSSS)评分。通过序列特异性引物聚合酶链反应进行基因分型。

结果

我们发现,等位基因DRB115和DQB103纯合基因型的携带者达到EDSS评分3的时间明显早于这些等位基因的非携带者(分别为p = 0.0172;p = 0.00183)。基因型DQB103/03的携带也与达到EDSS评分5所需的时间显著缩短相关(p = 0.00316)。在疾病持续5年时,DRB107等位基因的携带者的EDSS评分较低(p = 0.028)。当使用MSSS评分时,与疾病残疾进展为中等速度和快速的MS患者相比,进展缓慢的MS患者中基因型DRB1*15/15的频率较低(p = 0.0305)。

讨论

我们首次表明,HLA - DRB1和 - DQB1基因型是斯洛伐克MS患者残疾进展的遗传标志物。基因型DRB115/15和DQB103/03被确定为短期临床负面预后因素,而等位基因DRB107的携带似乎是MS更好预后的积极预后标志物。

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