Hashimoto L L, Walter M A, Cox D W, Ebers G C
Department of Clinical Neurological Sciences, University Hospital University of Western Ontario, London, Canada.
J Neuroimmunol. 1993 Apr;44(1):77-83. doi: 10.1016/0165-5728(93)90270-9.
In addition to the major histocompatibility complex (MHC), genetic susceptibility in multiple sclerosis (MS) appears to be influenced by other loci. A recent study has identified a population association with an immunoglobulin heavy chain variable region polymorphism in the VH2-B5 family, with both familial and sporadic MS patients. We have repeated this association study in a second MS patient group and used two ethnically and geographically matched control groups and the MS patients' unaffected sibs for comparisons. The VH2-B5 polymorphism was found to be over-represented in MS patients when compared to all three control groups. This VH2-B5 association was stronger when the MS patient data were combined with data from our previous study. To further explore the implications of this population association, MS sibships were analyzed for haplotype sharing by identity by descent (IBD) for VH2 and VH3f gene segment polymorphisms. The distribution of haplotype sharing did not differ from that expected based upon random segregation. The data are consistent with the IGVH locus exerting a minor effect perhaps by interacting with other loci to influence MS susceptibility or with genetic heterogeneity and a role for this complex in a subgroup of patients.
除主要组织相容性复合体（MHC）外，多发性硬化症（MS）的遗传易感性似乎还受其他基因座影响。最近一项研究发现，VH2 - B5家族中的免疫球蛋白重链可变区多态性与MS患者群体存在关联，包括家族性和散发性MS患者。我们在另一组MS患者中重复了这项关联研究，并使用了两个在种族和地理上匹配的对照组以及MS患者未患病的同胞进行比较。与所有三个对照组相比，发现VH2 - B5多态性在MS患者中过度呈现。当将MS患者数据与我们先前研究的数据合并时，这种VH2 - B5关联更强。为了进一步探究这种群体关联的意义，对MS同胞对进行了分析，以确定VH2和VH3f基因片段多态性的同源性单倍型共享情况。单倍型共享的分布与基于随机分离预期的情况没有差异。数据表明，IGVH基因座可能通过与其他基因座相互作用来影响MS易感性，或者与遗传异质性有关，并且该复合体在一部分患者中起作用，从而发挥较小的影响。
