Fernandez-Morera J L, Rodriguez-Rodero S, Tunon A, Martinez-Borra J, Vidal-Castineira J R, Lopez-Vazquez A, Rodrigo L, Rodrigo P, González S, Lahoz C H, Lopez-Larrea C
Histocompatibility and Transplant Unit, Hospital Universitario Central de Asturias, Oviedo, Spain.
Tissue Antigens. 2008 Jul;72(1):54-9. doi: 10.1111/j.1399-0039.2008.01066.x.
It has been widely reported that the major histocompatibility complex (MHC) class II region provides the main genetic contribution to multiple sclerosis (MS) susceptibility. However, recent studies have suggested that the MHC class I region may also contribute to the development of MS. In this study, we investigated the possible association of the human leukocyte antigen (HLA)-B, MHC class I chain-related gene B (MICB) and MHC class I chain-related gene A (MICA) genes, located in the MHC class I region, with MS susceptibility. For this purpose, we analyzed the distribution of HLA-DR, HLA-B, MICB and MICA alleles in 121 MS patients and 156 healthy controls. Neither HLA-B nor MICA alleles were found to be associated with MS susceptibility, and only the frequency of HLA-DRB101 allele was found to be increased in controls (31% vs 14%, P(c) = 0.011). However, MICB004 allele frequency was significantly increased in MS patients (46.3% vs 23.3%, P(c) < 0.001, odds ratio = 2.82, 95% confidence interval = 1.68-4.73). Although, MICB004 and HLA-DRB115 belong to the AH 7.1 ancestral haplotype, the association of MICB004 to MS susceptibility was found to be independent of HLA-DRB115 in our population. This and previous studies clearly suggest that the MHC class I, in addition to class II, could be involved in MS susceptibility.
已有广泛报道称，主要组织相容性复合体（MHC）II类区域对多发性硬化症（MS）易感性提供了主要的遗传贡献。然而，最近的研究表明，MHC I类区域也可能对MS的发展有影响。在本研究中，我们调查了位于MHC I类区域的人类白细胞抗原（HLA）-B、MHC I类链相关基因B（MICB）和MHC I类链相关基因A（MICA）基因与MS易感性之间的可能关联。为此，我们分析了121例MS患者和156例健康对照中HLA-DR、HLA-B、MICB和MICA等位基因的分布情况。未发现HLA-B和MICA等位基因与MS易感性相关，仅发现HLA-DRB101等位基因在对照中的频率增加（31%对14%，校正P值 = 0.011）。然而，MICB004等位基因频率在MS患者中显著增加（46.3%对23.3%，校正P值 < 0.001，优势比 = 2.82，95%置信区间 = 1.68 - 4.73）。尽管MICB004和HLA-DRB115属于AH 7.1祖先单倍型，但在我们的人群中发现MICB004与MS易感性的关联独立于HLA-DRB115。本研究及先前的研究清楚地表明，除了II类外，MHC I类也可能参与MS易感性。
