Servicio de Neurología, Hospital Clínico San Carlos, Ciudad Universitaria, Madrid, Spain.
Mult Scler. 2011 May;17(5):513-20. doi: 10.1177/1352458510393263. Epub 2010 Dec 21.
In a prior study of our group we found an up-regulation of CD46 expression in a cohort of Spanish multiple sclerosis (MS) patients.
To evaluate the potential role of CD46 in the response to interferon-beta treatment in MS patients through the analysis of five tagging single nucleotide polymorphisms (SNPs) and measurement of mRNA.
A total of 406 MS patients and 513 control patients were analysed for five SNPs at the CD46 locus. Furthermore, 163 MS patients and 163 matched control patients were analysed by RT-PCR for the CD46 mRNA expression in three blood samples (basal, and at 6 and 12 months of interferon-beta treatment) collected in the course of a 1-year follow-up.
Two genotypes of rs2724385 polymorphism (AT and TT) could be markers of response to interferon-beta therapy in MS patients (p=0.007 and p=0.006, respectively). Furthermore, the frequency of interferon-beta responders was 44.4% (32/72) in MS patients with an increased CD46 mRNA expression, vs. 65.9% (60/91) in patients with a decreased CD46 mRNA expression (p=0.006).
The present study shows that CD46 could be associated with the response to interferon-beta therapy; however, the genetic results should be replicated in an independent cohort and further studies are needed to confirm the role of CD46.
在我们小组的先前研究中，我们发现西班牙多发性硬化症（MS）患者群体中 CD46 表达上调。
通过分析五个标记单核苷酸多态性（SNP）和测量 mRNA，评估 CD46 在 MS 患者对干扰素-β治疗反应中的潜在作用。
对 406 名 MS 患者和 513 名对照患者进行了 CD46 基因座的五个 SNP 分析。此外，对 163 名 MS 患者和 163 名匹配对照患者进行了 RT-PCR 分析，以在为期 1 年的随访中收集的三个血液样本（基础、干扰素-β治疗 6 个月和 12 个月）中测量 CD46 mRNA 表达。
rs2724385 多态性的两种基因型（AT 和 TT）可作为 MS 患者对干扰素-β治疗反应的标志物（分别为 p=0.007 和 p=0.006）。此外，在 CD46 mRNA 表达增加的 MS 患者中，干扰素-β应答者的频率为 44.4%（32/72），而在 CD46 mRNA 表达降低的患者中，干扰素-β应答者的频率为 65.9%（60/91）（p=0.006）。
本研究表明 CD46 可能与干扰素-β治疗反应相关；然而，遗传结果需要在独立队列中复制，并且需要进一步的研究来确认 CD46 的作用。
