Increased susceptibility to rheumatoid arthritis in Koreans heterozygous for HLA-DRB1*0405 and*0901
Increased susceptibility to rheumatoid arthritis in Koreans heterozygous for HLA-DRB1*0405 and*0901
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DOI：
10.1002/art.20608
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发表时间：
2004-11-01
影响因子：
--
通讯作者：
Bae, SC
中科院分区：
文献类型：
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作者：
Lee, HS;Lee, KW;Bae, SC
Objective.研究亚洲人群中类风湿关节炎（RA）及其临床标志物与易感性和保护性HLA-DRB 1等位基因的相关性。所有RA患者（n = 574）和对照组（n = 392）均为韩国人。通过聚合酶链反应、序列特异性寡核苷酸探针杂交和直接DNA测序分析对所有等位基因进行HLA-DRB 1分型和进一步分型。采用相对倾向效应（RPE）法和错误发现率校正法进行多重比较。DRB 1 *0405和 *0901等位基因与RA的相关性最显著（P = 7.83 × 10（-24），比值比[OR] 4.40 [95% CI 3.24-5.99]和P = 3.76 × 10（-9），OR 2.47 [95% CI 1.82-3.36]）。RPEs试验显示DRB 1 *0401和 *0410等位基因赋予易感性，而DRB 1 *0701、*0802、*1301、*1302、*1403和 *1405等位基因表现出显著的保护作用。易感性和保护性等位基因都表现出与加性遗传效应一致的模式，并且各自独立地影响RA。复合杂合子DRB 1 *0405/*0901与RA的最高风险相关（校正P = 1.81 × 10（-11），OR 58.2 [95%CI 7.95-425.70]）。在至少有一个DRB 1 *0405或DRB 1 *0901等位基因拷贝的患者中，平均发病年龄分别提前4年或提前3年。影像学改变（II-IV期）在至少有1个DRB 1 *0405拷贝的患者中更常见（P = 0.032，92.6%vs 84.3%，OR 2.33 [95%CI 1.244.39]）。DRB 1 *0405/*0901杂合子与RA的相关性最强，表明该杂合子增强了韩国人对RA的易感性。
Objective. To investigate the association of susceptibility and protective HLA-DRB1 alleles with rheumatoid arthritis (RA) and its clinical markers in an Asian population.Methods. All RA patients (n = 574) and control subjects (n = 392) were Korean. HLA-DRB1 typing and further subtyping of all alleles was performed by polymerase chain reaction, sequence-specific oligonucleotide probe hybridization, and direct DNA sequencing analysis. We used a relative predispositional effects (RPEs) method and a false discovery rate correction method for multiple comparisons.Results. The DRB1*0405 and *0901 alleles showed the most significant associations with RA (P = 7.83 X 10(-24), odds ratio [OR] 4.40 [95% confidence interval (95% CI) 3.24-5.99], and P = 3.76 X 10(-9), OR 2.47 [95% CI 1.82-3.36], respectively). The RPEs test showed that the DRB1*0401 and *0410 alleles conferred susceptibility and that the DRBI*0701, *0802, *1301, *1302, *1403, and *1405 alleles showed significant protective effects. Susceptibility and protective alleles both showed a pattern consistent with additive genetic effects, and each influenced RA independently of the other. The compound heterozygote DRB1*0405/*0901 was associated with the highest risk of RA (corrected P = 1.81 X 10(-11), OR 58.2 [95% CI 7.95-425.70]). The mean age at disease onset was similar to4 years earlier or was 3 years earlier, respectively, in patients with at least 1 copy of the DRB1*0405 or the DRB1*0901 allele. Radiographic changes (stages II-IV were more frequent in patients with at least 1 copy of DRB1*0405 (P = 0.032, 92.6% versus 84.3%, OR 2.33 [95% CI 1.244.39]).Conclusion. The DRB1*0405/*0901 heterozygote has the strongest association with RA, suggesting that this heterozygote enhances the susceptibility to RA in Koreans.