The rs10492972 KIF1B polymorphism and disease progression in Greek patients with multiple sclerosis

Abstract

A recent genome-wide association study (GWAS) demonstrated an association of the rs10492972[C] variant of KIF1B with multiple sclerosis (MS) [1]. KIF1B encodes a kinesin superfamily member involved in mitochondrial axonal transport and may influence the ability of oligodendrocytes to remyelinate demyelinated axons [2, 3]. Impaired mitochondrial transport and chronic demyelination have been linked to axonal loss, which is important in the development of irreversible disability in MS [2, 4]. We therefore sought to investigate a possible influence of rs10492972 on disease progression in Greek MS patients. We studied 609 patients with MS [5]. Demographic and clinical data are shown in the table. Expanded disability status scale (EDSS) was measured in remission [6]. A total of 243 patients received disease-modifying therapy. MS severity score (MSSS) was determined in 562 patients (disease duration[1 year) [7]. The control group consisted of 230 healthy subjects (mean age 38.1 ± 10.7 years, 121 women). Patients and controls gave written informed consent for molecular genetic studies. DNA was isolated from peripheral blood using standard NaCl extraction. Genotyping of rs10492972 was performed with a standard PCR protocol (primers: 50 GGATACAAGGGGTGGTGA 30, 50 AAGTTATGTGGCCAGGA 30). MboII restriction of the 112-bp product resulted in Tand C-alleles (T-allele: 67 and 45-bp products; C-allele: 112-bp product). Statistical comparisons between patients and controls and between patients with different genotypes were performed using Chi-square, ANOVA, Mann–Whitney, and Kruskal–Wallis tests, as appropriate. Kaplan–Meier analysis (log-rank test) was used to assess the effect of genotypes on time to sustained disability. Analysis was performed with SPSS software. Genotype distribution in patients and controls was in Hardy–Weinberg equilibrium (p = 0.31 and 0.65). C-allele frequency was 0.31 in both patients and controls. There was no difference in allelic or genotype frequencies between patients and controls (p = 0.99 and 1.0). MSSS and time to EDSS 4.0 (Fig. 1) or 6.0 were not significantly