DRB1*03:01 haplotypes: differential contribution to multiple sclerosis risk and specific association with the presence of intrathecal IgM bands.
DRB1*03:01 haplotypes: differential contribution to multiple sclerosis risk and specific association with the presence of intrathecal IgM bands.
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DOI：
10.1371/journal.pone.0031018
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Núñez C
中科院分区：
文献类型：
--
作者：
de la Concha EG;Cavanillas ML;Cénit MC;Urcelay E;Arroyo R;Fernández Ó;Álvarez-Cermeño JC;Leyva L;Villar LM;Núñez C
多发性硬化症 (MS) 是一种具有遗传基础的多因素疾病。与该疾病最强的关联在于人类白细胞抗原（HLA）区域。然而，除了迄今为止与 MS 相关的主要危险因素 DRB1*15:01 等位基因外，尚未描述任何其他变异的一致效应。一个例子是 HLA-DRB1*03:01，它在不同人群和研究中具有异质性效应。我们假设这些差异可能是由于携带该等位基因的不同单倍型的差异造成的。因此，我们的目的是研究 DRB1*03:01 与 MS 易感性的关联，考虑到该等位基因在全球范围内并按单倍型分层。我们还评估了脑脊液中针对髓磷脂脂质 (OCMB) 的寡克隆 IgM 条带的存在与否的关联。对 1068 名 MS 患者和 624 名种族匹配的健康对照者进行了 HLA-B、-DRB1 和 -DQA1 基因分型。根据 OCMB 的存在（M+，58 名患者）/不存在（M−，81 名患者）对 139 名 MS 患者进行分类。使用卡方检验或 Fisher 精确检验进行组间比较（MS 患者与对照组以及 M+ 与 M−）。观察到 DRB1*03:01 与 MS 易感性的关联，但具有不同的单倍型贡献，祖先单倍型 (AH) 18.2 是导致最高风险的一种。 M+、M− 和对照之间的比较表明，AH 18.2 仅影响 M+ 个体，带来与 DRB1*15:01 引起的风险类似的风险。包含 DRB1*03:01 的不同单倍型对 MS 易感性具有不同的风险。 AH 18.2 造成的风险最高，并且仅影响显示 OCMB 的个人。
Multiple sclerosis (MS) is a multifactorial disease with a genetic basis. The strongest associations with the disease lie in the Human Leukocyte Antigen (HLA) region. However, except for the DRB1*15:01 allele, the main risk factor associated to MS so far, no consistent effect has been described for any other variant. One example is HLA-DRB1*03:01, with a heterogeneous effect across populations and studies. We postulate that those discrepancies could be due to differences in the diverse haplotypes bearing that allele. Thus, we aimed at studying the association of DRB1*03:01 with MS susceptibility considering this allele globally and stratified by haplotypes. We also evaluated the association with the presence of oligoclonal IgM bands against myelin lipids (OCMB) in cerebrospinal fluid. Genotyping of HLA-B, -DRB1 and -DQA1 was performed in 1068 MS patients and 624 ethnically matched healthy controls. One hundred and thirty-nine MS patients were classified according to the presence (M+, 58 patients)/absence (M−, 81 patients) of OCMB. Comparisons between groups (MS patients vs. controls and M+ vs. M−) were performed with the chi-square test or the Fisher exact test. Association of DRB1*03:01 with MS susceptibility was observed but with different haplotypic contribution, being the ancestral haplotype (AH) 18.2 the one causing the highest risk. Comparisons between M+, M− and controls showed that the AH 18.2 was affecting only M+ individuals, conferring a risk similar to that caused by DRB1*15:01. The diverse DRB1*03:01-containing haplotypes contribute with different risk to MS susceptibility. The AH 18.2 causes the highest risk and affects only to individuals showing OCMB.
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影响因子：
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通讯作者：
TOURTELLOTTE, WW
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