Lin R, Taylor B V, Charlesworth J, van der Mei I, Blizzard L, Stewart N, Ponsonby A-L, Dwyer T, Pittas F, Simpson S
Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tas., Australia; Guangxi Center for Disease Prevention and Control, Nanning, China.
Acta Neurol Scand. 2015 Apr;131(4):231-9. doi: 10.1111/ane.12315. Epub 2014 Oct 14.
To investigate whether those genes involved in the vitamin D pathway modulate the relationship between 25-hydroxyvitamin D (25(OH)D) and IFN-β, the relationship between IFN-β and sun in predicting 25(OH)D, and the interaction between IFN-β and 25(OH)D in modulating relapse risk in patients with MS.
Prospective cohort study of 169 participants with MS and genotype data followed 2002-2005. Gene-IFN-β and gene-IFN-β-sun interactions predicting 25(OH)D evaluated by multilevel mixed-effects linear regression. Gene-IFN-β interactions with 25(OH)D in modulating in relapse risk assessed using survival analysis.
The cohort was 71.6% female and of mean age 47.8. Two-independent intronic genotyped SNPs (rs10767935 and rs5030244) in WT1 significantly modified the IFN-β-25(OH)D association after adjustment (P(interaction) = 0.001, 0.0002; P(adj) = 0.003, 0.006, respectively). There was a marked difference in the interaction between self-reported sun exposure and IFN-β in predicting 25(OH)D by level of rs10767935, although this did not reach statistical significance. No SNPs modified the interaction between IFN-β and 25(OH)D in predicting relapse.
We have demonstrated that two-independent SNPs (rs10767935 and rs5030244) in WT1 modified the IFN-β-25(OH)D association in patients with MS. Some evidence was shown for a difference in the sun-IFN-β-25(OH)D association by level of rs10767935. These findings indicate that WT1 variants may play a role in altering the effects of IFN-β on vitamin D in MS.
研究参与维生素D途径的那些基因是否会调节25-羟基维生素D（25(OH)D）与干扰素-β（IFN-β）之间的关系、IFN-β与阳光在预测25(OH)D方面的关系，以及IFN-β与25(OH)D在调节多发性硬化症（MS）患者复发风险中的相互作用。
对169名患有MS且有基因分型数据的参与者进行2002 - 2005年的前瞻性队列研究。通过多级混合效应线性回归评估基因 - IFN-β以及基因 - IFN-β - 阳光之间预测25(OH)D的相互作用。使用生存分析评估基因 - IFN-β与25(OH)D在调节复发风险中的相互作用。
该队列中女性占71.6%，平均年龄47.8岁。WT1基因中两个独立的内含子基因分型单核苷酸多态性（SNP，rs10767935和rs5030244）在调整后显著改变了IFN-β - 25(OH)D的关联（交互作用P值分别为0.001、0.0002；调整后P值分别为0.003、0.006）。根据rs10767935水平，自我报告的阳光暴露与IFN-β在预测25(OH)D方面的相互作用存在显著差异，尽管未达到统计学显著性。在预测复发方面，没有SNP改变IFN-β与25(OH)D之间的相互作用。
我们已经证明，WT1基因中的两个独立SNP（rs10767935和rs5030244）改变了MS患者中IFN-β - 25(OH)D的关联。有一些证据表明，根据rs10767935水平，阳光 - IFN-β - 25(OH)D的关联存在差异。这些发现表明，WT1基因变体可能在改变IFN-β对MS中维生素D的作用方面发挥作用。
