ANN RHEUM DIS:全基因组关联和功能研究确定了基质Gla蛋白在手部骨关节炎中的作用

2017-09-20 xiangting MedSci原创

MGP变体与手部OA的风险升高之间的关联是由MGP的表达下降引起的,这可能通过减少对软骨钙化的抑制而增加了手部OA的负担。

骨关节炎(OA)是关节炎最常见的形式,也是导致老年人残疾的主要原因。在所有关节中,手部OA的遗传易感性最强;然而,已被确认的手部OA遗传风险基因位点很少。这项研究的目标是确定与手部OA相关的新基因,并探讨其潜在的机制。

研究人员在12784名个体中进行了一项全基因组关联的手OA研究(发现组:8743,复制组:4011)。通过分析人类关节软骨的RNA测序数据集(n = 96)中的基因和等位基因特异性表达,对全基因组重要信号进行跟踪。

在发现组中发现了两个显著相关的位点:在基质Gla蛋白(MGP)基因附近的chr12(p = 3.5×10 -10)和CCDC91基因附近的chr12 (p = 6.1×10 -9)。MGP基因附近的DNA变体在另外三项研究中得到验证,这导致了MGP变体与手OA之间的高度显著的相关性(rs4764133,Beta meta = 0.83,P meta = 1.8*10-15)。该变体与MGP中的编码变体维生素K依赖性软骨钙化抑制剂高度连锁不平衡。使用人原发性软骨组织(n = 96)的RNA测序数据,观察到与参考等位基因的MGP RNA表达相比,手部OA风险等位基因的MGP RNA表达显著降低(40.7%,p<5*10-16)。

该研究结果表明,MGP变体与手部OA的风险升高之间的关联是由MGP的表达下降引起的,这可能通过减少对软骨钙化的抑制而增加了手部OA的负担。

原始出处:

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    2018-08-12 lisa438
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    2017-09-22 lmm397
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