人类补体第四成分的遗传多态性：基于Rodgers和Chido决定簇的基因组PCR分型的群体研究及修订命名法建议。

Schneider P M, Stradmann-Bellinghausen B, Rittner C

Institute of Forensic Medicine, Johannes Gutenberg University, Mainz, Germany.

Eur J Immunogenet. 1996 Oct;23(5):335-44. doi: 10.1111/j.1744-313x.1996.tb00006.x.

The fourth component of human complement (C4) is coded for by two homologous genes, C4A and C4B, located in the class III region of the major histocompatibility complex (MHC). Genetic typing of C4A and B alleles is routinely carried out by high-voltage agarose gel electrophoresis. The electrophoretic C4 polymorphism can be further subdivided by the Rodgers (Rg) and Chido (Ch) blood groups, which are antigenic determinants of the C4A and B alpha-chains, respectively. We have used a recently described direct PCR typing method using sequence-specific primers (PCR-SSP) in combination with electrophoretic C4 typing as well as genomic RFLP analysis to determine the frequency of C4 allotypes, Rg/Ch subtypes and C4A-B haplotypes in a family study of the German population. As the current C4 allele designation does not provide any information about the presence or absence of Rodgers and Chido antigens, we have developed an extension to the existing C4 nomenclature. This revised allele designation combines the existing numerical allotypes defined by electrophoretic mobility with eight subtypes (01-08) based on Rg/Ch PCR genotyping results. Using this approach, most electrophoretic allotypes could be subdivided. Among the C4A allotypes, the most common allele was A0301 (59.9%), and the most common subtype among all electrophoretic allotypes was 01 (85.1%; = Rg1,2-positive, Ch-negative). For C4B, the most common allele was B0101 (64.3%), and the most common subtype was 01 (79.6%; = Ch1,2,3,4,5,6-positive, Rg-negative). The subtypes 03, 04, 07 and 08 of the C4A allotypes, and the subtypes 03, 07 and 08 of the C4B allotypes, were not detected in this study. The analysis of duplicated C4 alleles revealed considerable heterogeneity of their subtypes. The results demonstrate that all known C4 allotypes can now be assigned unambiguously, which facilitates the identification of MHC haplotypes relevant for transplantation and disease association studies.

人类补体的第四成分（C4）由位于主要组织相容性复合体（MHC）Ⅲ类区域的两个同源基因C4A和C4B编码。C4A和B等位基因的基因分型通常通过高压琼脂糖凝胶电泳进行。电泳C4多态性可通过Rodgers（Rg）和Chido（Ch）血型进一步细分，它们分别是C4A和Bα链的抗原决定簇。我们使用了最近描述的一种直接PCR分型方法，即序列特异性引物PCR（PCR - SSP），结合电泳C4分型以及基因组RFLP分析，来确定德国人群家族研究中C4同种异型、Rg/Ch亚型和C4A - B单倍型的频率。由于当前的C4等位基因命名没有提供关于Rodgers和Chido抗原存在与否的任何信息，我们对现有的C4命名法进行了扩展。这种修订后的等位基因命名将由电泳迁移率定义的现有数字同种异型与基于Rg/Ch PCR基因分型结果的八个亚型（01 - 08）相结合。使用这种方法，大多数电泳同种异型都可以细分。在C4A同种异型中，最常见的等位基因是A0301（59.9%），在所有电泳同种异型中最常见的亚型是01（85.1%；= Rg1,2阳性，Ch阴性）。对于C4B，最常见的等位基因是B0101（64.3%），最常见的亚型是01（79.6%；= Ch1,2,3,4,5,6阳性，Rg阴性）。本研究未检测到C4A同种异型的03、04、07和08亚型，以及C4B同种异型的03、07和08亚型。对重复C4等位基因的分析揭示了其亚型的显著异质性。结果表明，现在可以明确地指定所有已知的C4同种异型，这有助于识别与移植和疾病关联研究相关的MHC单倍型。