New classification of HLA-DRB1 alleles in rheumatoid arthritis susceptibility: a combined analysis of worldwide samples.
New classification of HLA-DRB1 alleles in rheumatoid arthritis susceptibility: a combined analysis of worldwide samples.
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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。
DOI：
10.1186/ar2379
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发表时间：
2008
影响因子：
4.9
通讯作者：
Gourraud PA
中科院分区：
文献类型：
--
作者：
Barnetche T;Constantin A;Cantagrel A;Cambon-Thomsen A;Gourraud PA
类风湿性关节炎（RA）是一种病因不明的复杂多基因疾病。HLA-DRB 1等位基因编码的共享表位（SE）（DRβ1链第三高变区第72 - 74位的RAA氨基酸模式）与RA易感性相关。Tezenas du Montcel及其同事开发了一种新的HLA-DRB 1 SE等位基因分类，以细化HLA-DRB 1与RA之间的关联。在本研究中，我们使用了在全球范围内收集的RA样本，以调查这种新的HLA-DRB 1分类在不同高加索和非高加索患者中RA易感性方面的相关性。从759个病例和789个对照中确定了18个子样本，并根据其种族来源分为10个样本。根据新的HLA-DRB 1等位基因分类法，将HLA-DRB 1等位基因分为S1、S2、S3 D、S3 P和X五组。整个分析是通过比较10个高加索人和非高加索人样本中RA患者和对照组之间5个HLA-DRB 1等位基因组的携带者频率来进行的。荟萃分析的Mantel-Haenszel方法提供了总体比值比（OR）估计值和95%置信区间（CI）。S2等位基因携带者（OR 2.15，95%CI 1.54 ~ 3.00; p < 10-5）和S3 P等位基因携带者（OR 2.74，95%CI 2.01 ~ 3.74; p < 10-5）与RA易感性呈正相关。发现S1等位基因（OR 0.60，95%CI 0.48 ~ 0.76; p < 10-4）和X等位基因（OR 0.58，95%CI 0.39 ~ 0.84; p = 4 × 10-3）呈负相关。S3 D组等位基因无显著相关性（OR 0.89，95% CI 0.69 - 1.14; p = 0.89）。互补基因型分析符合先前报告的白种人RA患者的基因型风险等级。到目前为止，本研究是第一次尝试调查这一新的HLA-DRB 1分类在高加索和非高加索样本的RA易感性方面的相关性。我们的研究结果支持不同的HLA-DRB 1等位基因组在不同种族背景的RA易感性中发挥不同作用的假设，并证实了这种HLA-DRB 1分类在区分易感性和保护性等位基因方面的意义。
Rheumatoid arthritis (RA) is a complex polygenic disease of unknown etiology. HLA-DRB1 alleles encoding the shared epitope (SE) (RAA amino acid pattern in positions 72 to 74 of the third hypervariable region of the DRβ1 chain) are associated with RA susceptibility. A new classification of HLA-DRB1 SE alleles has been developed by Tezenas du Montcel and colleagues to refine the association between HLA-DRB1 and RA. In the present study, we used RA samples collected worldwide to investigate the relevance of this new HLA-DRB1 classification in terms of RA susceptibility across various Caucasoid and non-Caucasoid patients. Eighteen subsamples were defined from a total number of 759 cases and 789 controls and grouped in 10 samples on the basis of their ethnic origin. HLA-DRB1 alleles were divided into five groups (S1, S2, S3D, S3P, and X) according to the new HLA-DRB1 allele classification. The whole analysis was performed by comparing carrier frequencies for the five HLA-DRB1 allele groups between RA patients and controls across the 10 Caucasoid and non-Caucasoid samples. The Mantel-Haenszel method of meta-analysis provided a global odds ratio (OR) estimate with 95% confidence interval (CI). A positive association with RA susceptibility was found for S2 allele carriers (OR 2.15, 95% CI 1.54 to 3.00; p < 10-5) and S3P allele carriers (OR 2.74, 95% CI 2.01 to 3.74; p < 10-5). A negative association was found for S1 alleles (OR 0.60, 95% CI 0.48 to 0.76; p < 10-4) and X alleles (OR 0.58, 95% CI 0.39 to 0.84; p = 4 × 10-3). No significant association was highlighted for the S3D group of alleles (OR 0.89, 95% CI 0.69 to 1.14; p = 0.89). The complementary genotype analysis fit with the genotype risk hierarchy previously reported in Caucasoid RA patients. So far, the present study is the first attempt to investigate the relevance of this new HLA-DRB1 classification in terms of RA susceptibility on both Caucasoid and non-Caucasoid samples. Our results support the hypothesis of a differential role played by different HLA-DRB1 allele groups in RA susceptibility across different ethnic backgrounds and confirm the interest of such an HLA-DRB1 classification in differentiating predisposing and protective alleles.
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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：
14.9
作者：
Wheeler, David L.;Barrett, Tanya;Yaschenko, Eugene
通讯作者：
Yaschenko, Eugene
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作者：
Kochi, Y;Yamada, R;Yamamoto, K
通讯作者：
Yamamoto, K
影响因子：
64.8
作者：
Chanock, Stephen J.;Manolio, Teri;Collins, Francis S.
通讯作者：
Collins, Francis S.
影响因子：
2.7
作者：
Zanelli, E;Breedveld, FC;de Vries, RRP
通讯作者：
de Vries, RRP