Different patterns of associations with anti-citrullinated protein antibody-positive and anti-citrullinated protein antibody-negative rheumatoid arthritis in the extended major histocompatibility complex region.
Different patterns of associations with anti-citrullinated protein antibody-positive and anti-citrullinated protein antibody-negative rheumatoid arthritis in the extended major histocompatibility complex region.
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DOI：
10.1002/art.24135
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发表时间：
2009-01
影响因子：
--
通讯作者：
Klareskog, Lars
中科院分区：
文献类型：
--
作者：
Ding, Bo;Padyukov, Leonid;Lundstrom, Emeli;Seielstad, Mark;Plenge, Robert M.;Oksenberg, Jorge R.;Gregersen, Peter K.;Alfredsson, Lars;Klareskog, Lars
为了确定主要组织相容性复合物（MHC）区域中的其他变异，该区域在根据存在或不存在柠檬酸蛋白抗原（ACPA）的抗体抗体的类风湿关节炎（RA）疾病子群（RA）的风险。
在使用无与伦比的分析和匹配的分析来调整HLA – DRB1基因型的多步分析策略中，我们分析了2,221个单核苷酸多态性（SNP），跨越10.7 MB，从6p22.2到6p22.2到6p21.31阳性RA，我们分析了瑞典流行病学研究类风湿关节炎（EIRA）和北美类风湿关节炎的样本联盟（NARAC）研究（总计1,255例病例和1,719个对照）。
对于ACPA阳性RA，总共有299个SNP达到了范围范围的显着性（P <2.3×10-5），而令人惊讶的是，对于ACPA阴性RA，没有SNP达到这种意义。风险等位基因并确定了与HLA – DPB1附近SNP的其他独立关联（RS3117213；优势比1.42 [95％置信区间1.17-1.73]，Pcombin = 0.0003的牢固关联）。
根据ACPA状态定义的2种疾病子集的MHC关联有明显的遗传模式。 RA。
To identify additional variants in the major histocompatibility complex (MHC) region that independently contribute to risk in 2 disease subsets of rheumatoid arthritis (RA) defined according to the presence or absence of antibodies to citrullinated protein antigens (ACPAs). In a multistep analytical strategy using unmatched as well as matched analyses to adjust for HLA–DRB1 genotype, we analyzed 2,221 single-nucleotide polymorphisms (SNPs) spanning 10.7 Mb, from 6p22.2 to 6p21.31, across the MHC. For ACPA-positive RA, we analyzed samples from the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA) and the North American Rheumatoid Arthritis Consortium (NARAC) studies (totaling 1,255 cases and 1,719 controls). For ACPA-negative RA, we used samples from the EIRA study (640 cases and 670 controls). Plink and SAS statistical packages were used to conduct all statistical analyses. A total of 299 SNPs reached locus-wide significance (P < 2.3 × 10−5) for ACPA-positive RA, whereas surprisingly, no SNPs reached this significance for ACPA-negative RA. For ACPA-positive RA, we adjusted for known DRB1 risk alleles and identified additional independent associations with SNPs near HLA–DPB1 (rs3117213; odds ratio 1.42 [95% confidence interval 1.17–1.73], Pcombined = 0.0003 for the strongest association). There are distinct genetic patterns of MHC associations in the 2 disease subsets of RA defined according to ACPA status. HLA–DPB1 is an independent risk locus for ACPA-positive RA. We did not identify any associations with SNPs within the MHC for ACPA-negative RA.
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影响因子：
4.9
作者：
Winchester R
通讯作者：
Winchester R
影响因子：
9.8
作者：
Kallberg, Henrik;Padyukov, Leonid;Alfredsson, Lars
通讯作者：
Alfredsson, Lars
影响因子：
158.5
作者：
Plenge, Robert M.;Seielstad, Mark;Gregersen, Peter K.
通讯作者：
Gregersen, Peter K.
影响因子：
4.4
作者：
Ota, M;Katsuyama, Y;Inoko, H
通讯作者：
Inoko, H
类风湿关节炎易感性中HLA-DRB1等位基因的新分类：全球样品的组合分析。
影响因子：
4.9
作者：
Barnetche T;Constantin A;Cantagrel A;Cambon-Thomsen A;Gourraud PA
通讯作者：
Gourraud PA