Clu Polymorphisms and Plasma Clusterin Levels in Patients With Multiple Sclerosis: Association With Disability Scores, Progression Rate and Fingolimod Therapy

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-na & iuml;ve 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-na & iuml;ve 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.