骨桥蛋白在杜氏肌萎缩症(S15.002)

文摘

摘要目的:测试的效果SPP1 rs28357094纵向队列的动态DMD患者和解剖的分子机制增加rs28357094与G等位基因相关疾病严重程度。

背景骨桥蛋白(OPN编码SPP1基因)是一个由多个细胞类型包括肌母细胞分泌糖蛋白表达。在mdx通过减少肌肉OPN调节炎症和纤维化改变生长因子b (TGFB)。在杜氏肌营养不良症(DMD)的多态性SPP1启动子区域(rs28357094)疾病进展的是一个决定因素。

设计/方法:80 rs28357094 DMD患者基因分型和分层TT和TG / GG根据主导模式。基因型比较表型使用动态评估北极星(NSAA)和6分钟步行试验(6 mwt)得分在T0和病人。肌肉活检的患者选择的量化研究TGFB和转化生长因子b受体2 (TGFBR2)信使rna和SPP1信使rna和蛋白质、肌肉组织学和浸润炎症细胞。的多态性TGFBR2基因(rs4522809)基因分型的患者。

结果:两NSAA配对t检验显示出显著性差异(p = 0.013)和6 mwt (p = 0.03)之间的基线和随访12个月后DMD患者携带G等位基因。T组差异不显著。OPN在DMD肌肉调节。没有明显的骨桥蛋白mRNA和蛋白表达的差异也没有TGFB和TGFBR2G和T基因型之间的信使rna rs28357094被发现。增加CD4 +和CD68细胞在T等位基因携带者rs28357094被观察到。TGFBR2rs4522809多态性预测SPP1信使rna水平。

结论:SPP1基因型是一种强大的疾病修饰符在DMD和可以作为协变量相关模式的临床试验。OPN和调节炎症变化TGFBR2基因型预测骨桥蛋白在DMD肌肉。

披露:Pegoraro博士已经收到个人活动与补偿BioMarin制药公司和梅达制药公司。贝罗博士没有披露。Piva博士没有披露。Barp博士没有披露。Ermani博士没有披露。Politano博士没有披露。麦古利博士已经收到个人补偿活动Aceleron制药和PTC疗法,inc .) / Genzyme公司。麦古利博士已经收到了个人在一篇社论中补偿神经肌肉疾病的能力,神经病学年鉴,发育医学与儿童神经病学>上发表和Neuropediatrics。首页麦古利博士收到电视节目研究支持意大利和欧洲SMA。Previtali博士没有披露。多浪迪警官博士没有披露。 Dr. Bruno has nothing to disclose. Dr. Minetti has nothing to disclose. Dr. Berardinelli has nothing to disclose. Dr. Comi has received research support from Telethon Italy and SMA Europe. Dr. D'Amico has nothing to disclose. Dr. Soraru' has nothing to disclose. Dr. Messina has nothing to disclose. Dr. Mongini has received personal compensation for activities with Telethon Italy and Genzyme Corporation. Dr. Mogini has received research support from AIFA and Telethon Italy. Dr. Bertini has received personal compensation for activities with Telethon Italy and SMA Europe. Dr. Ferlini has nothing to disclose. Dr. Gualandi has nothing to disclose. Dr. Battini has nothing to disclose. Dr. Boffi has nothing to disclose. Dr. Pane has nothing to disclose. Dr. Vita has nothing to disclose. Dr. Hoffman has received personal compensation for activities with investment bankers as a consultant.Dr. Hoffman has received (royalty or license fee or contractual rights) payments from Children's Hospital Boston.Dr. Hoffman holds stock and/or stock options in ReveraGen Biopharma, which sponsored research in which Dr. Hoffman was involved as an investigator. Dr. Angelini has received personal compensation for activities with Genzyme Corporation.