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使用计算方法分析风湿性关节炎中血管内皮生长因子-A (VEGF-A) 多态的关联分析

Iraj Ahmed¹, Peter John², Attya Bhatti³

¹Atta-Ur-Rehman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad, Pakistan.

Scientific reports

|December 11, 2023

概括

这项研究确定了血管内皮生长因子A (VEGFA) 的有害遗传变异,这些变异有助于类风湿性关节炎 (RA). 这些突变会影响VEGFAFA.

科学领域:

分子生物学分子生物学
遗传学遗传学是一个
免疫学免疫学免疫学

背景情况:

类风湿性关节炎 (RA) 涉及关节炎症,骨形成,软骨破坏和骨质侵蚀.
突性增生和血管生成是RA病理的标志,观察到血管内皮生长因子A (VEGFA) 的增加.
维格法 (VEGFA) 是一种促血管性因素,在RA中被上调,这表明它在疾病发病过程中的作用.

研究的目的:

调查功能性和致病性VEGFA变异及其对RA易感性和严重性的影响.
分析VEGFA中的点突变对其与VEGFR2.2相互作用的影响.
用计算方法评估VEGFA多态的结构和功能后果.

主要方法:

使用in silico预测工具和保护性分析,从168个nsSNP中识别了致病性VEGFA变异.
模拟了VEGFA变异,对VEGFR2域 (IGD2,IGD3) 进行对接,并使用分子动力学 (Gromacs) 模拟.
进行了蛋白质-蛋白质对接 (STRING数据库) 和稳定性分析 (HOPE,Ramachandran图,ERRAT).

主要成果:

在168个nsSNP中,有19个被确定为高度致病性.
大多数突变降低了VEGFA蛋白的稳定性,破坏位于关键功能领域的nsSNP.
突变R108Q与VEGFR2的稳定性增加,而R82Q,C86Y和R108W与野生类型VEGFA相比稳定性降低.

结论:

致病性VEGFA变种可以改变蛋白质结构和功能,影响类风湿性关节炎.
特定的VEGFA突变影响其与VEGFR2的相互作用,可能影响疾病的易感性和严重程度.
已识别的高风险VEGFA变异值得考虑在类风湿性关节炎患者中进行遗传查.

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