Gallina R, Bottaro A, Boccazzi C, DeLange G, Danese P, Mazzola G, Amoroso A, DeMarchi M, Carbonara A O
Dipartimento di Genetica, Biologia e Chimica medica, Torino, Italy.
Eur J Immunol. 1992 Jan;22(1):227-33. doi: 10.1002/eji.1830220133.
IgG4 deficiency is very common (1/400 in the Italian population) and provides a good model for analyzing the genetic factors involved in Ig subclass deficiencies. We have previously reported an association between some immunoglobulin heavy chain constant region (IGHC) polymorphisms and the IgG4 deficiency. The associated polymorphisms spanned the region between the GP and the G4 genes. A larger sample composed of 50 healthy blood donors with IgG4 deficiency (less than 0.001 g/l IgG4), not carrying homozygous gene deletions, together with 82 first-degree relatives is now examined. The results confirmed the association of the deficiency with IGHC polymorphisms, and detected a new association with the HLA-D locus with a strong additive effect between the two systems. However, despite these associations and a highly significant risk for IgG4 deficiency within families, close linkage with either IGHC or HLA loci was not apparent by the affected sib pair method. These findings suggest that several concomitant, possibly cooperating, genetic factors may be involved in IgG4 deficiency.
IgG4缺乏非常常见（在意大利人群中为1/400），为分析参与Ig亚类缺乏的遗传因素提供了一个良好的模型。我们之前报道了一些免疫球蛋白重链恒定区（IGHC）多态性与IgG4缺乏之间的关联。相关多态性跨越了GP基因和G4基因之间的区域。现在对一个更大的样本进行了检测，该样本由50名IgG4缺乏（IgG4低于0.001 g/l）且未携带纯合基因缺失的健康献血者以及82名一级亲属组成。结果证实了该缺乏与IGHC多态性的关联，并检测到与HLA - D位点的新关联，且两个系统之间存在强烈的累加效应。然而，尽管存在这些关联以及家族内IgG4缺乏的高度显著风险，但通过患病同胞对法并未发现与IGHC或HLA位点的紧密连锁。这些发现表明，IgG4缺乏可能涉及多个同时存在、可能相互协作的遗传因素。
