DNA Methylation of the MHC Region in Rheumatoid Arthritis: Perspectives and Challenges
DNA Methylation of the MHC Region in Rheumatoid Arthritis: Perspectives and Challenges
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类风湿关节炎中 MHC 区域的 DNA 甲基化：前景和挑战
DOI：
10.3899/jrheum.191404
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发表时间：
2020-11
影响因子：
3.9
通讯作者：
Yun Liu
中科院分区：
文献类型：
--
作者：
Wenqing Qiu;Yun Liu
MHC位于6p21.3位点，面积约4mb，是人类基因组中多态性最多的区域之一。拥有200多个基因的高密度，其中大多数直接参与对自身或非自身抗原的免疫反应，MHC基因长期以来与广泛的复杂人类疾病有关，包括自身免疫性或炎症性疾病和癌症。类风湿性关节炎（RA）是一种全身性自身免疫性疾病；最近利用单核苷酸多态性进行的大型全基因组关联研究证实，在许多人群中，经典HLA基因和非经典HLA基因与RA存在相关性1,2。功能和结构分析表明，这些遗传变异存在于肽结合槽中，可能影响瓜氨酸化肽的结合亲和力，最终导致RA1,3的发展。然而，由于种族和临床亚型的异质性，MHC中主要ra风险等位基因在不同人群中存在较大差异。例如，HLA-DRB1*04包括*04:01和*04:04等位基因，这是白人的主要RA风险等位基因4，而DRB1*04:05/*0901是亚洲人的主要RA风险等位基因，特别是抗纤氨酸化蛋白抗体（ACPA）阳性的RA患者5,6。最近……
The MHC, which covers a region about 4 Mb at 6p21.3, is one of the most polymorphic regions in the human genome. With a high density of more than 200 genes, most of which are directly involved in the immune response to self or non-self antigens, MHC genes have long been associated with a wide range of complex human diseases, including autoimmune or inflammatory diseases and cancer. Rheumatoid arthritis (RA) is a systemic autoimmune disease; recent investigations in large genome-wide association studies using single-nucleotide polymorphisms have confirmed the correlation of classic HLA genes and non-classic HLA genes with RA in many populations1,2. Functional and structural analyses indicate that these genetic variants reside in the peptide-binding groove, which may affect the binding affinity of the citrullinated peptides, and eventually lead to the development of RA1,3. However, because of the heterogeneity among ethnic groups and clinical subtypes, the major RA-risk allele in MHC is quite different among different populations. For example, HLA-DRB1*04 includes the *04:01 and *04:04 alleles, which are the dominant RA-risk alleles in whites4, whereas DRB1*04:05/*0901 are the major RA-risk alleles in Asians, specifically for RA patients positive for anticitrullinated protein antibodies (ACPA)5,6. A recent …
Address correspondence to W. Qiu or Y. Liu, 130 Dong An Road, Shanghai, China. Email: qiuwq{at}fudan.edu.cn; yliu39{at}fudan.edu.cn.
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影响因子：
--
作者：
Lee, HS;Lee, KW;Bae, SC
通讯作者：
Bae, SC
影响因子：
12.8
作者：
Kindt, Alida S. D.;Fuerst, Rainer W.;Bonifacio, Ezio
通讯作者：
Bonifacio, Ezio
影响因子：
16.6
作者：
Kular L;Liu Y;Ruhrmann S;Zheleznyakova G;Marabita F;Gomez-Cabrero D;James T;Ewing E;Lindén M;Górnikiewicz B;Aeinehband S;Stridh P;Link J;Andlauer TFM;Gasperi C;Wiendl H;Zipp F;Gold R;Tackenberg B;Weber F;Hemmer B;Strauch K;Heilmann-Heimbach S;Rawal R;Schminke U;Schmidt CO;Kacprowski T;Franke A;Laudes M;Dilthey AT;Celius EG;Søndergaard HB;Tegnér J;Harbo HF;Oturai AB;Olafsson S;Eggertsson HP;Halldorsson BV;Hjaltason H;Olafsson E;Jonsdottir I;Stefansson K;Olsson T;Piehl F;Ekström TJ;Kockum I;Feinberg AP;Jagodic M
通讯作者：
Jagodic M
影响因子：
3
作者：
Ka S;Lee S;Hong J;Cho Y;Sung J;Kim HN;Kim HL;Jung J
通讯作者：
Jung J
DOI：
10.1074/jbc.h118.001829
发表时间：
2018-03
期刊：
The Journal of Biological Chemistry
影响因子：
--
作者：
D. Margulies
通讯作者：
D. Margulies