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The level of interleukin-10 (IL-10) expression is related to polymorphisms -1082 (G/A), -819 (T/C) and -592 (A/C) in the promoter region of the IL-10 gene, which constitute three haplotypes, GCC, ATA, and ACC. The ATA (a non-GCC) haplotype, which is associated with low IL-10 expression, has been shown to improve interferon (IFN) treatment response in hepatitis C. We analysed the distribution of IL-10 promoter haplotype combinations to determine whether they could influence initial IFN treatment response in 63 patients with relapsing-remitting multiple sclerosis (MS). The patients were grouped into non-GCC or GCC haplotypes, and the clinical and magnetic resonance imaging (MRI) disease activity was compared in the two groups. During the first 6 months of treatment, MS patients with non-GCC haplotypes experienced fewer new MRI T1-contrast enhancing lesions [0.77+/-0.36 (SEM)] than patients with the GCC haplotype (2.45+/-0.57) (P=0.05, Mann-Whitney U test). No differences were detected on clinical disease activity. The results suggest an influence of IL-10 promoter polymorphisms on IFN treatment response in MS.

Background It has been suggested that polymorphisms in the WT1 gene modulate the effect of IFN- β treatment in multiple sclerosis ( MS) through regulation of the relationship between IFN- β and vitamin D. Objective To examine whether WT1 modulates the relationship between IFN- β and vitamin D in a longitudinal study with repeated assessment of vitamin D before and after initiation of IFN- β. Methods In a prospective study of 85 patients with relapsing remitting MS, 25-hydroxyvitamin D was measured at month 0, 1, 3, 6, 7, 9, 12, 18 and 24. None of the patients used any immunomodulatory treatment at inclusion, and all started IFN- β treatment at month 6. Results The mean concentrations of seasonally adjusted 25-hydroxyvitamin increased slightly (3.1 ± 1.2 nmol/l, P = 0.008) after initiation of IFN- β. The association between IFN- β treatment and 25-hydroxyvitamin D was similar in patients carrying any of the two alleles in the WT1 SNPs (rs10767935 and rs5030244) recently reported to modulate this relationship. Conclusions In this prospective study with repeated measurements of 25-hydroxyvitamin D before and during treatment with IFN- β, we did not find that genetic variation in WT1 plays any role in regulating the relationship between IFN- β and serum 25-hydroxyvitamin D. [ABSTRACT FROM AUTHOR]