Influence of HLA-DRB1 alleles on the susceptibility and resistance to multiple sclerosis in Japanese patients with respect to anti-aquaporin 4 antibody status
Influence of HLA-DRB1 alleles on the susceptibility and resistance to multiple sclerosis in Japanese patients with respect to anti-aquaporin 4 antibody status
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DOI：
10.1177/1352458509355067
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发表时间：
2010-02-01
影响因子：
5.8
通讯作者：
Kira, J.
中科院分区：
文献类型：
--
作者：
Isobe, N.;Matsushita, T.;Kira, J.
背景：人类白细胞抗原（HLA）-DRB 1等位基因间的上位相互作用改变了高加索人多发性硬化（MS）的风险。这种相互作用从未在亚洲MS patients.Objective：探讨HLA-DRB 1等位基因的影响，包括上位性相互作用在这个位点，在日本MS患者与抗水通道蛋白4（AQP 4）antibody.Methods：HLA-DRB 1基因分型在108例MS患者和127名健康对照。根据抗AQP 4抗体状态，将MS患者进一步分为两组（27例阳性，81例阴性）。结果：HLA-DRB1*09（校正比值比（OR）= 0.243，95%置信区间（CI）0.099-0.533）和HLA-DRB 1 *01 HLA-DRB 1 *12增加抗AQP 4抗体阳性MS的风险（校正OR = 3.691，95%CI 1.233-10.565）。携带HLA-DRB 1 *09/15的个体降低了抗AQP 4抗体阴性MS的风险（调整OR = 0.164，95%CI 0.026-0.593），而HLA-DRB 1 *12/15增加了抗AQP 4抗体阳性MS的风险结论：HLA-DRB 1 *09降低抗AQP 4抗体阴性MS风险的能力可能源于与HLA-DRB 1 *15的相互作用。相比之下，HLA-DRB 1 *12可能通过与HLA-DRB 1 *15的相互作用增加对抗AQP 4抗体阳性MS的易感性。
Background: Epistatic interactions between human leukocyte antigen (HLA)-DRB1 alleles alter multiple sclerosis (MS) risk in Caucasians. Such interactions have never been studied in Asian MS patients.Objective: To investigate the influence of HLA-DRB1 alleles, including epistatic interactions at this locus, in Japanese MS patients with and without the anti-aquaporin 4 (AQP4) antibody.Methods: The HLA-DRB1 locus was genotyped in 108 MS patients and 127 healthy controls. MS patients were further classified into two groups according to anti-AQP4 antibody status (27 positive and 81 negative).Results: HLA-DRB1*09 (adjusted odds ratio (OR) = 0.243, 95% confidence interval (CI) 0.099-0.533) and HLA-DRB1*01 (adjusted OR = 0.327, 95% CI 0.103-0.873) decreased the incidence of anti-AQP4 antibody-negative MS. By contrast, HLA-DRB1*12 increased the risk of anti-AQP4 antibody-positive MS (adjusted OR = 3.691, 95% CI 1.233-10.565). Individuals with HLA-DRB1*09/15 decreased the risk of anti-AQP4 antibody-negative MS (adjusted OR = 0.164, 95% CI 0.026-0.593), while those with HLA-DRB1*12/15 increased the risk of anti-AQP4 antibody-positive MS (adjusted OR = 10.870, 95% CI 2.004-81.752).Conclusions: The ability of HLA-DRB1*09 to reduce the risk of anti-AQP4 antibody-negative MS may arise from an interaction with HLA-DRB1*15. By contrast, HLA-DRB1*12 increases susceptibility to anti-AQP4 antibody-positive MS, possibly via an interaction with HLA-DRB1*15.