CLU polymorphisms and plasma clusterin levels in patients with multiple sclerosis: association with disability scores, progression rate and fingolimod therapy.

IF 1.7 4区医学 Q3 CLINICAL NEUROLOGY

Neurological Research Pub Date : 2025-04-27 DOI:10.1080/01616412.2025.2497477

Osman Oğuzhan Kılıç, Semra Mungan, Şeref Demirkaya, Birsen Can Demirdöğen

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引用次数: 0

Abstract

Objectives: Multiple sclerosis (MS) is a chronic, demyelinating disorder of the central nervous system that is widely accepted to result from a complex interplay of genetic and environmental factors. The involvement of clusterin in neurodegenerative and autoimmune diseases has been highlighted, but its role in MS remains unclear. This study aimed to investigate the association of four single nucleotide polymorphisms (SNPs) in the clusterin gene (CLU) with MS susceptibility.

Methods: The study group consisted of 310 patients with RRMS (pwRRMS) and 310 controls. 25 treatment-naïve pwRRMS, 25 pwRRMS on fingolimod treatment and 25 controls composed a subgroup for further analysis. The genotypes of 4 CLU SNPs were determined using either restriction endonuclease digestion following PCR (rs11136000 & rs3087554) or the real-time PCR method using TaqMan genotyping assays (rs2279590 & rs1532278). Plasma clusterin concentration was determined by ELISA in the subgroup (n = 75).

Results: Our results revealed that CLU rs3087554 C allele (p = .008) and TC + CC genotype were significantly associated with RRMS (p = .002). Furthermore, haplotype analysis has also shown that T-C-T-T haplotype was associated with RRMS (p < .001). Moreover, plasma clusterin concentrations were significantly higher in pwRRMS on fingolimod therapy compared to treatment-naïve pwRRMS and the control group. In addition, plasma clusterin concentration was increased in patients with rs11136000 & rs1532278 CC genotypes in the subgroup.

Discussion: These findings suggest that CLU SNPs and plasma clusterin concentrations could serve as significant biomarkers at different stages of MS.

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多发性硬化症患者CLU多态性和血浆聚集蛋白水平：与残疾评分、进展率和fingolimod治疗相关

目的：多发性硬化症（MS）是一种慢性中枢神经系统脱髓鞘疾病，被广泛认为是遗传和环境因素复杂相互作用的结果。聚簇蛋白在神经退行性疾病和自身免疫性疾病中的作用已被强调，但其在多发性硬化症中的作用仍不清楚。本研究旨在探讨聚簇基因（CLU）中4个单核苷酸多态性（SNPs）与MS易感性的关系。方法：研究组由310例RRMS患者（pwRRMS）和310例对照组组成。25名treatment-naïve pwRRMS， 25名芬戈莫德治疗组pwRRMS和25名对照组组成亚组进行进一步分析。采用限制性内切酶酶切PCR法（rs11136000和rs3087554）或TaqMan基因分型法（rs2279590和rs1532278）测定4个CLU snp的基因型。采用ELISA法测定亚组患者血浆聚簇素浓度（n = 75）。结果：CLU rs3087554 C等位基因（p = 0.008）和TC + CC基因型与RRMS显著相关（p = 0.002）。此外，单倍型分析也显示T-C-T-T单倍型与RRMS相关(p)。这些发现表明CLU snp和血浆聚集蛋白浓度可以作为MS不同阶段的重要生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neurological Research 医学-临床神经学

CiteScore

3.60

自引率

0.00%

发文量

116

审稿时长

5.3 months

期刊介绍： Neurological Research is an international, peer-reviewed journal for reporting both basic and clinical research in the fields of neurosurgery, neurology, neuroengineering and neurosciences. It provides a medium for those who recognize the wider implications of their work and who wish to be informed of the relevant experience of others in related and more distant fields. The scope of the journal includes: •Stem cell applications •Molecular neuroscience •Neuropharmacology •Neuroradiology •Neurochemistry •Biomathematical models •Endovascular neurosurgery •Innovation in neurosurgery.