Genetic polymorphism of HLA-DR in the Japanese population.

F Obata
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Abstract

As a result of carrying out sequence analyses on the HLA-DR genes of several Japanese donors, we found three new DRB1 alleles, DRB1-12b, DRB1-14c, and DRB1-JX6, that had not been identified using immunological procedures. Sequence-specific oligonucleotide (SSO) probes directed against various DRB1 alleles, including the above three, enabled DNA typing of all the DRB types in the Japanese population and calculation of their gene frequencies based on this typing to be carried out for the first time. The SSO-DNA typing yielded higher DR13 and DR14 gene frequencies than those reported by serological workshops. Next, we applied this DR-DNA typing to the analysis of Japanese patients with juvenile rheumatoid arthritis (JRA) and found that DRB1*0405 was the allele susceptible to rheumatoid factor-positive polyarticular JRA, which is one of the four types of JRA that has been classified clinically. Analysis of the DR types of patients who suffered unexplained recurrent spontaneous abortion (URSA) using DNA typing demonstrated that 1) URSA is not correlated with any particular DR type and 2) no difference between the DR sharing rate of patients and normal couple was detected, which contradicts the results obtained in some serological studies.

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日本人群HLA-DR基因多态性研究。
通过对几个日本供者的HLA-DR基因进行序列分析,我们发现了三个新的DRB1等位基因,DRB1-12b、DRB1-14c和DRB1- jx6,这些等位基因没有通过免疫学方法被鉴定出来。针对多种DRB1等位基因(包括上述三种等位基因)的序列特异性寡核苷酸(SSO)探针,首次实现了日本人群中所有DRB型的DNA分型,并基于该分型计算其基因频率。SSO-DNA分型比血清学研讨会报告的DR13和DR14基因频率更高。接下来,我们将这种DR-DNA分型应用于日本幼年类风湿性关节炎(JRA)患者的分析,发现DRB1*0405是类风湿因子阳性多关节型JRA的易感等位基因,是临床上已分类的四种JRA类型之一。对不明原因复发性自然流产(URSA)患者的DR类型进行DNA分型分析表明:1)URSA与任何特定DR类型无关;2)患者与正常夫妇的DR共享率无差异,这与一些血清学研究的结果相矛盾。
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