The impact of HLA-DRB1 genes on extra-articular disease manifestations in rheumatoid arthritis.
The impact of HLA-DRB1 genes on extra-articular disease manifestations in rheumatoid arthritis.
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DOI：
10.1186/ar1837
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发表时间：
2005
影响因子：
4.9
通讯作者：
Matteson EL
中科院分区：
文献类型：
--
作者：
Turesson C;Schaid DJ;Weyand CM;Jacobsson LT;Goronzy JJ;Petersson IF;Sturfelt G;Nyhäll-Wåhlin BM;Truedsson L;Dechant SA;Matteson EL
本研究的目的是检测严重关节外类风湿关节炎(EXRA)患者的人类白细胞抗原-DRB1和人类白细胞抗原-DQB1基因分型，并与无关节外表现的类风湿关节炎(RA)患者进行比较。严重的类风湿性关节炎患者来自一个大型的类风湿性关节炎患者研究数据库，从两个流行的类风湿性关节炎病例队列中招募，从一个地区性多中心早期类风湿关节炎队列中招募。有外露表现者159例，按预先确定的标准进行分类。178例类风湿性关节炎(RA)患者作为对照，无EXRA。病例组和对照组在RA病程和临床中心方面匹配。用Biotest SSP试剂盒进行基于聚合酶链式反应的人类白细胞抗原-DRB1和人类白细胞抗原-DQB1基因分型，并进行测序以区分DRB1*04亚型。通过对等位基因随机分布的多次模拟，检验了等位基因与疾病表型之间的关联。HLADRB1和HLADQB1等位基因在EXRA患者和对照组之间的全球分布差异无统计学意义。FERTY综合征组DRB1*0401(P=0.003)和0401/0401纯合子(P=0.002)频率明显高于对照组。编码共同表位(SE)的两个HLA-DRB1*04等位基因的存在与外周症状(总优势比1.79，95%可信区间1.04-3.08)和类风湿血管炎(优势比2.44，95%可信区间1.22-4.89)相关。在这一大样本的EXRA患者中，Felty综合征是唯一明显与HLA-DRB1*0401相关的表现。其他外显性表现与DRB1*04 SE双剂量型无关，而与个体等位基因有关。这证实了SE基因与RA疾病的严重程度和EXRA有关。其他遗传和环境因素可能会对个体的Exra表现产生更具体的影响。
The objective of this study was to examine HLA-DRB1 and HLA-DQB1 genotypes in patients with severe extra-articular rheumatoid arthritis (ExRA) and to compare them with the genotypes of rheumatoid arthritis (RA) patients without extra-articular manifestations. Patients with severe ExRA were recruited from a large research database of patients with RA, from two cohorts of prevalent RA cases, and from a regional multicenter early RA cohort. Cases with ExRA manifestations (n = 159) were classified according to predefined criteria. Controls (n = 178) with RA but no ExRA were selected from the same sources. Cases and controls were matched for duration of RA and for clinical center. PCR based HLA-DRB1 and HLA-DQB1 genotyping was performed using the Biotest SSP kit, with additional sequencing in order to distinguish DRB1*04 subtypes. Associations between alleles and disease phenotypes were tested using multiple simulations of random distributions of alleles. There was no difference in global distribution of HLA-DRB1 and HLA-DQB1 alleles between patients with ExRA and controls. DRB1*0401 (P = 0.003) and 0401/0401 homozygosity (P = 0.002) were more frequent in Felty's syndrome than in controls. The presence of two HLA-DRB1*04 alleles encoding the shared epitope (SE) was associated with ExRA (overall odds ratio 1.79, 95% confidence interval 1.04–3.08) and with rheumatoid vasculitis (odds ratio 2.44, 95% confidence interval 1.22–4.89). In this large sample of patients with ExRA, Felty's syndrome was the only manifestation that was clearly associated with HLA-DRB1*0401. Other ExRA manifestations were not associated with individual alleles but with DRB1*04 SE double dose genotypes. This confirms that SE genes contribute to RA disease severity and ExRA. Other genetic and environmental factors may have a more specific impact on individual ExRA manifestations.
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影响因子：
5
作者：
SCHNEIDER, HA;YONKER, RA;PANUSH, RS
通讯作者：
PANUSH, RS
影响因子：
--
作者：
Martens, PB;Goronzy, JJ;Weyand, CM
通讯作者：
Weyand, CM
影响因子：
--
作者：
Gabriel, SE;Crowson, CS;Matteson, EL
通讯作者：
Matteson, EL
影响因子：
5.5
作者：
Coakley, G;Brooks, D;Lanchbury, JS
通讯作者：
Lanchbury, JS
影响因子：
5.9
作者：
GORDON, DA;STEIN, JL;BRODER, I
通讯作者：
BRODER, I