Walter M A, Gibson W T, Ebers G C, Cox D W
Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
J Clin Invest. 1991 Apr;87(4):1266-73. doi: 10.1172/JCI115128.
15 immunoglobulin heavy chain constant (CH) and variable region (VH) polymorphisms were selected to span the entire length of the heavy chain cluster. These polymorphisms were examined in 34 sib pairs concordant for multiple sclerosis (MS) and in 23 sporadic MS patients. Allele frequencies were calculated for the 2 MS patient groups and compared with those found in a control population from the same geographical location and of similar ethnic background. No significant association was found between MS and the 7 CH region polymorphisms examined. However, a significant correlation between the MS phenotype and a VH2 family polymorphism was observed in both MS patient populations (familial MS patients chi 2 = 8.16, P less than 0.005; sporadic MS patients chi 2 = 8.90, P less than 0.005). One allele of the VH2-5 gene segment was found to be over-represented in both MS groups. VH2-5 has recently been physically mapped close to the CH region, between 180 and 360 kb away. These results indicate that a locus near or within the CH-proximal VH region is associated with increased susceptibility to MS.
选择了15个免疫球蛋白重链恒定区（CH）和可变区（VH）多态性位点，以覆盖重链基因簇的全长。在34对患多发性硬化症（MS）的同胞对以及23例散发型MS患者中检测了这些多态性。计算了这两组MS患者的等位基因频率，并与来自相同地理位置、种族背景相似的对照人群中的等位基因频率进行比较。在所检测的7个CH区域多态性位点与MS之间未发现显著关联。然而，在两组MS患者群体中均观察到MS表型与VH2家族多态性之间存在显著相关性（家族性MS患者χ2 = 8.16，P < 0.005；散发型MS患者χ2 = 8.90，P < 0.005）。在两个MS组中均发现VH2-5基因片段的一个等位基因出现频率过高。VH2-5最近已在物理图谱上定位到靠近CH区域的位置，距离为180至360 kb。这些结果表明，CH近端VH区域附近或内部的一个基因座与MS易感性增加有关。
