Joseph病黄氏家系与HLA关联的研究

对Joseph病黄氏家系中25人(包括患者11人)检测了HLA-A、B位点抗原分型,其中18人作了Bf和C4的检测。发现Bf均为F型、C4均为C4A3和C4B1,因此不能提供分离信息。根据A、B位点抗原分析出单倍型,发现有两种HLA单倍型,HLA-A11、B13和HLAA30、B13始终伴随着患者。根据目前材料计算Lods值为1,27,呈松弛的连锁关系,而此病又呈现出明确的显性遗传,因此推测本病除MHC区外至少还存在有一个以上的调节基因。另外发现没有A11、B13或A30、B13单倍型者均不发病,这一负相关可作为非疾病基因携带者的标志。

A FAMILY STUDY ON JOSEPH DISEASE ASSOCIATED WITH HLA

A large five generation family inherited with dominant Joseph disease was found in the area of Jing-Jin-Tang in China. 25 individuals including 11 patients were typed for HLA-A and B antigens and 18 of them were tested for Bf and C4. There was no significant information found from Bf and C4 because all the Bf appeared BfF and C4 were C4A3 and C4B1. HLA haplotype were analysed from their antigens and another 10 individuals' haplotypes including 4 patients were deduced according to the pedigree. It was found that the distribution of their HLA antigens and haplotypes in 10 small families of 4 generations were considerable simple. It was noticed that two haplotypes: HLA-A11, B13 and HLA-A30, B13 were accompanied in all of the patients. From present data we can not judge whether HLA-A 11, B13 and HLA-A30, B13 came from different parents or due to cross over from two haplotypes in same parent. The Lods score according to the former hypothesis supported that this disease may loosely associated with HLA-A11, B13 and it would be even more closely linked with this haplotype if the Lods calculation is based on the later hypothese. Although there is contradictory with the later hypothesis because of too high ratio of crossover exists, it should be noticed that the haplotype of HLA-A11, B13 was very rare in normal Chinese population, so it is unlikely that the haplotype of HLA-A11, B13 came form normal population gene pool but came from crossover. The Lods value at present is rather low therefore it is hard to determine whether the linkage of Joseph disease with HLA was positive or negative. The fact of dominant inherity of this disease indicates that there must be at least more than one regulation gene other then HLA associated with this disease. The fact that all the HLA-A11, B13 and HLA-A30, B13 (-) carrier were healthy without exception is interesting and it leads a good association marker to non-disease carrier.