Analysis of HLA-DRB1 polymorphisms in Japanese patients with primary biliary cirrhosis (PBC): The HLA-DRB1 polymorphism determines the relative risk of antinuclear antibodies for disease progression in PBC
Analysis of HLA-DRB1 polymorphisms in Japanese patients with primary biliary cirrhosis (PBC): The HLA-DRB1 polymorphism determines the relative risk of antinuclear antibodies for disease progression in PBC
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DOI：
10.1111/j.1872-034x.2010.00631.x
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发表时间：
2010-05-01
影响因子：
4.2
通讯作者：
Ishibashi, Hiromi
中科院分区：
文献类型：
--
作者：
Nakamura, Minoru;Yasunami, Michio;Ishibashi, Hiromi
目的：抗gp210抗体和抗着丝粒抗体是原发性胆汁性肝硬化(PBC)进展的不同危险因素。结果：抗gp210(优势比46.56，95%可信区间9.20~850.1)和抗着丝粒抗体(OR，2.36，95%CI，1.28~4.35)分别是PBC进展的危险因素。HLA-DRB1*0405和*0803易产生抗gp210抗体(OR，1.61，95%CI，1.08~2.39)和抗着丝粒抗体(OR，2.30，95%CI，1.41~3.73)。HLA-DRB1*1502和*0901患者易发生非黄床型进展(OR，1.98，95%CI，1.13~3.40 AND OR，1.78，95%CI，1.02~3.03)，而HLA-DRB1*0803和*0405患者易发生疾病进展(OR，2.24，95%CI，1.48~3.41和OR，1.53，95%CI，1.11~2.11)。根据HLA-DRB1等位基因对患者进行分层显示，抗gp210抗体是一个强大的危险因素，无论是否存在导致黄褐型进展的HLA-DRB1等位基因，而抗着丝粒抗体是非黄褐型进展的显著危险因素。在患者中，抗着丝粒抗体是非黄褐型进展的显著危险因素。结论：HL A-DRB1基因多态性不仅与疾病的发生和发展有关，而且与抗核抗体的产生和确定导致PBC疾病进展的相对风险有关。
Aims: Anti-gp210 and anti-centromere antibodies are different risk factors for the progression of primary biliary cirrhosis (PBC). However, the association of human leukocyte antigen (HLA) polymorphisms with these risk factors is unknown.Methods: We determined the HLA-DRB1 genotype in 334 Japanese PBC patients and studied their serum antibodies to gp210 and centromere during the 1-452-month observation period.Results: Anti-gp210 (odds ratio [OR] 46.56, 95% confidence interval [CI], 9.20-850.1) and anti-centromere antibodies (OR, 2.36, 95% CI, 1.28-4.35) were significant risk factors for jaundice-and nonjaundice-type progression, respectively. HLA-DRB1*0405 and *0803 predisposed patients to anti-gp210 (OR, 1.61, 95% CI, 1.08-2.39) and anti-centromere (OR, 2.30, 95% CI, 1.41-3.73) antibody production, respectively. HLA-DRB1*1502 and *0901 patients were predisposed to nonjaundice-type progression (OR, 1.98, 95% CI, 1.13-3.40 and OR, 1.78, 95% CI, 1.02-3.03), while HLA-DRB1* 0803 and *0405 patients were predisposed to disease development (OR, 2.24, 95% CI, 1.48-3.41 and OR, 1.53, 95% CI, 1.11-2.11, respectively). Stratifying patients by HLA-DRB1 alleles revealed that anti-gp210 antibodies was a strong risk factor, regardless of the HLA-DRB1 alleles for jaundice-type progression, while anti-centromere antibodies was a significant risk factor for nonjaundice-type progression in patients HLA-DRB1*0405 ( OR, 6.89, 95% CI, 2.18-26.56) and -DRB1*0803 ( OR, 5.42, 95% CI, 1.47-24.62) but not other HLA-DRB1 alleles.Conclusions: HLA-DRB1 polymorphisms are significantly associated with not only disease development and progression but also antinuclear antibody production and the determination of the relative risk of antinuclear antibodies that contribute to PBC disease progression.