Anticitrullinated protein antibody (ACPA) in rheumatoid arthritis: influence of an interaction between HLA-DRB1 shared epitope and a deletion polymorphism in glutathione S-transferase in a cross-sectional study.
Anticitrullinated protein antibody (ACPA) in rheumatoid arthritis: influence of an interaction between HLA-DRB1 shared epitope and a deletion polymorphism in glutathione S-transferase in a cross-sectional study.
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DOI：
10.1186/ar3190
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发表时间：
2010
影响因子：
4.9
通讯作者：
Gregersen PK
中科院分区：
文献类型：
--
作者：
Mikuls TR;Gould KA;Bynoté KK;Yu F;Levan TD;Thiele GM;Michaud KD;O'Dell JR;Reimold AM;Hooker R;Caplan L;Johnson DS;Kerr G;Richards JS;Cannon GW;Criswell LA;Noble JA;Bridges SL Jr;Hughes L;Gregersen PK
谷胱甘肽S-转移酶Mu-1（GSTM 1-null）的缺失多态性以前曾被认为在类风湿性关节炎（RA）的风险和进展中发挥作用，尽管以前没有研究过它与抗瓜氨酸蛋白抗体（ACPA）阳性的相关性。本研究的目的是研究GSTM 1-null与ACPA阳性RA的相关性，并评估GSTM 1与HLA-DRB 1共享表位（SE）之间相互作用的证据。在两个RA队列中分别检查了GSTM 1-null与ACPA阳性的相关性，即退伍军人事务部风湿性关节炎（VARA）登记处（n = 703）和新发RA研究（索诺拉; n = 610）。通过计算归因于相互作用的比例（AP）来检查相互作用。VARA登记研究（76%）和索诺拉（69%）中的大多数患者ACPA阳性，GSTM 1-null（分别为53%和52%）和HLA-DRB 1 SE阳性（分别为76%和71%）的频率相似。VARA登记研究中吸烟患者的参数（80%）比索诺拉（65%）更常见。在VARA登记研究中，GSTM 1-null与ACPA阳性显著相关（比值比（OR），1.45; 95%置信区间（CI），1.02 - 2.05），但在索诺拉中不相关（OR，1.00; 95% CI，0.71 - 1.42）。在VARA登记研究中，ACPA阳性的GSTM 1和HLA-DRB 1 SE之间存在显著的相加相互作用（AP，0.49; 95%CI，0.21至0.77; P < 0.001），索诺拉中也存在这种相互作用（AP，0.38; 95%CI，0.00至0.76; P = 0.050）。这项研究首次表明，GSTM 1-null基因型，一种常见的遗传变异，施加显着的加性交互作用与HLA-DRB 1 SE的ACPA阳性的风险在RA。由于GSTM 1具有已知的抗氧化功能，这些数据表明，氧化应激可能是重要的RA特异性自身免疫性遗传易感个体的发展。
A deletion polymorphism in glutathione S-transferase Mu-1 (GSTM1-null) has previously been implicated to play a role in rheumatoid arthritis (RA) risk and progression, although no prior investigations have examined its associations with anticitrullinated protein antibody (ACPA) positivity. The purpose of this study was to examine the associations of GSTM1-null with ACPA positivity in RA and to assess for evidence of interaction between GSTM1 and HLA-DRB1 shared epitope (SE). Associations of GSTM1-null with ACPA positivity were examined separately in two RA cohorts, the Veterans Affairs Rheumatoid Arthritis (VARA) registry (n = 703) and the Study of New-Onset RA (SONORA; n = 610). Interactions were examined by calculating an attributable proportion (AP) due to interaction. A majority of patients in the VARA registry (76%) and SONORA (69%) were positive for ACPA with a similar frequency of GSTM1-null (53% and 52%, respectively) and HLA-DRB1 SE positivity (76% and 71%, respectively). The parameter of patients who had ever smoked was more common in the VARA registry (80%) than in SONORA (65%). GSTM1-null was significantly associated with ACPA positivity in the VARA registry (odds ratio (OR), 1.45; 95% confidence interval (CI), 1.02 to 2.05), but not in SONORA (OR, 1.00; 95% CI, 0.71 to 1.42). There were significant additive interactions between GSTM1 and HLA-DRB1 SE in the VARA registry (AP, 0.49; 95% CI, 0.21 to 0.77; P < 0.001) in ACPA positivity, an interaction replicated in SONORA (AP, 0.38; 95% CI, 0.00 to 0.76; P = 0.050). This study is the first to show that the GSTM1-null genotype, a common genetic variant, exerts significant additive interaction with HLA-DRB1 SE on the risk of ACPA positivity in RA. Since GSTM1 has known antioxidant functions, these data suggest that oxidative stress may be important in the development of RA-specific autoimmunity in genetically susceptible individuals.
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DOI：
10.1111/j.1744-313x.1991.tb00005.x
发表时间：
1991-02-01
期刊：
EUROPEAN JOURNAL OF IMMUNOGENETICS
影响因子：
--
作者：
ERLICH, H;BUGAWAN, T;WALSH, PS
通讯作者：
WALSH, PS
影响因子：
9.9
作者：
Mann, CLA;Davies, MB;Hawkins, CP
通讯作者：
Hawkins, CP
影响因子：
--
作者：
Mattey, DL;Hutchinson, D;Strange, RC
通讯作者：
Strange, RC
影响因子：
--
作者：
Lundstrom, Erneli;Kallberg, Henrik;Alfredsson, Lars;Klareskog, Lars;Padyukov, Leonid
通讯作者：
Padyukov, Leonid
影响因子：
--
作者：
Jawaheer, Damini;Lum, Raymond F.;Criswell, Lindsey A.
通讯作者：
Criswell, Lindsey A.