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	The amino acid variation within the binding pocket 7 and 9 of HLA-DRB1 molecules are associated with primary Sjögren's syndrome
	Renliang Huang ; Huang RL(黄仁良) ; Junping Yin ; Yan Chen ; Fengyuan Deng ; Juan Chen ; Xing Gao ; Zuguo Liu ; Xinhua Yu ; Junfeng Zheng ; Zheng JF(郑俊峰)
	2015-01-09
关键词	Autoimmunity HLA Homology modeling Peptide binding groove Sjögren's syndrome
英文摘要	在这篇论文当中，郑俊峰博士领导的课题小组发现在人白细胞抗原二类基因（HLA-II）中，HLA-DRB1*0803是中国南方原发干燥综合征易感基因。进一步通过结构生物信息学模拟DRB1*0803 分子结构并分析，发现HLA的抗原肽结合槽口袋9的表面电势的不同，可能是疾病易感性差异的分子基础。自身免疫病是由遗传因素和环境因素共同导致的疾病，在遗传因素里，HLA位点是很多自身免疫病的主要易感基因。但是，尽管HLA和自身免疫病的相关性非常明确，这种相关背后的机理还不清楚。这项关于HLA和干燥综合征相关性的研究在这一问题上做出了探索性的发现，对HLA和干燥综合征的相关的机制提出了新的观点。该成果也是自身免疫学实验室在干燥综合征方向上陆续发表的第4篇学术论文。; Primary Sjögren's syndrome (pSS) is associated with HLA-DRB1 loci, but the association of amino acid variations in the hypervariable region of the HLA-DR β1 chain with pSS is largely unknown. In this study, we aimed to identify the amino acid variations within the hypervariable region of HLA-DRB1 molecule which are associated with the susceptibility to pSS. We sequenced the 2nd exon of the HLA-DRB1 locus in 52 pSS patients and 179 controls. The HLA-DRB1*0803 is the allele that shows the strongest association with pSS in Chinese population (OR = 3.0, P = 2.4 × 10 −4 ). Furthermore, amino acid variations within the binding pocket P7 and P9 are associated with the susceptibility to pSS. An interaction between two residues within P7, β47 and β67, is associated with pSS. Structural modeling studies demonstrated that the electrostatics of peptide binding pocket 9 are opposite in pSS-susceptible and -protective HLA-DRB1 alleles. In conclusion, our results suggest that structural heterogeneity of the HLA-DRB1 peptide binding pocket P7 and P9 might play a role in the pathogenesis of pSS.
语种	英语
出版者	Elsevier Ltd.
内容类型	期刊论文
源URL	[http://dx.doi.org/10.1016/j.jaut.2014.11.006]
专题	医学院－已发表论文
推荐引用方式 GB/T 7714	Renliang Huang,Huang RL,Junping Yin,et al. The amino acid variation within the binding pocket 7 and 9 of HLA-DRB1 molecules are associated with primary Sjögren's syndrome[J],2015.
APA	Renliang Huang.,黄仁良.,Junping Yin.,Yan Chen.,Fengyuan Deng.,...&郑俊峰.(2015).The amino acid variation within the binding pocket 7 and 9 of HLA-DRB1 molecules are associated with primary Sjögren's syndrome..
MLA	Renliang Huang,et al."The amino acid variation within the binding pocket 7 and 9 of HLA-DRB1 molecules are associated with primary Sjögren's syndrome".(2015).

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