J Rheumatol:多个NOTCH4外显子突变与系统性硬化症的关联

2018-11-22 xiangting MedSci原创

多个NOTCH4外显子突变与SSc和/或SSc亚型相关。

既往的全基因组关联研究结果表明 NOTCH4基因与系统性硬化症(SSc)相关。这是一项后续研究,旨在精确定位SSc中的NOTCH4外显子突变。

使用Ion Torrent系统对1006名SSc患者和1004名美国白人对照的NOTCH4所有外显子进行测序和分析。通过Sanger测序来确认发现的SSc相关突变,然后在一个由576名SSc患者和574名对照组成的中国汉族队列中进行检查。分析了NOTCH4突变与SSc整体的关联,以及在伴/不伴已被确定为SSc主要遗传因素的特定HLA-II类等位基因影响下,与SSc临床和自身抗体亚型的关联。

在美国队列中共鉴定出12个SSc相关性和SSc亚型相关性NOTCH4外显子突变。其中3个是非同义单核苷酸多态性,1个是编码聚亮氨酸的CTG串联重复序列,所有这些都位于NOTCH4 细胞外结构域(NECD)。SSc相关HLA-II类等位基因的条件性logistic回归分析表明,NOTCH4突变与SSc自身抗体亚型独立相关。对中国队列的分析支持NOTCH4对SSc及其亚型的遗传影响。

多个NOTCH4外显子突变与SSc和/或SSc亚型相关。这些突变中的一些编码NECD的非同义序列改变,这意味着NOTCH4的潜在功能影响。

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    2018-11-24 karmond
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    2018-11-24 ymljack
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