HLA-DQβ遗传多态与重症肌无力的易患性

The polymorphism of HLA DQ β chain and genetic susceptibility to myasthenia gravis in Chinese

目的探讨ＨＬＡＤＱβ对重症肌无力（ＭＧ）的遗传易患性。方法采用聚合酶链反应限制片段长度多态性（ＰＣＲＲＦＬＰ）法对３５例ＭＧ患者及５０名健康对照ＨＬＡＤＱβ链对应的ＨＬＡＤＱＢ１基因进行分型，并对患者组和健康对照组的ＤＱＢ１各等位基因频率和ＤＱβ氨基酸序列进行比较分析。结果ＤＱＢ１０２０１和ＤＱＢ１０３０２的频率在患者组中升高，其中两组的ＤＱＢ１０３０２的频率差异具有显著性意义（ＲＲ＝４．４１，Ｐ＜０．０５）；ＨＬＡＤＱβ氨基端５７位的丙氨酸在患者组中显著升高（ＲＲ＝５．１０，Ｐ＜０．００５），在伴有胸腺瘤的ＭＧ患者中差异更显著（ＲＲ＝５７．８８，Ｐ＜０．００１）。结论ＨＬＡＤＱβ５７位的丙氨酸表现对中国人ＭＧ的易患性，特别是在伴有胸腺瘤的ＭＧ患者。这种易患性的遗传基础为非极性的疏水氨基酸丙氨酸替换了带负电荷的极性氨基酸天冬氨酸。

Objective To investigate the HLA DQ β genetic susceptibility to myasthenia gravis(MG) in Chinese. Methods Polymerase chain reaction restriction fragment length polymorphism (PCR RFLP) was used to determine the HLA DQB1 genotype of 35 MG patients and 50 healthy controls. Subsequently the frequency of HLA DQB1 alleles and the amino acid sequences of the HLA DQ β polymorphic aminoteriminal domain were compared between the MG patients and the healthy controls. Results The frequency of DQB1 *0302 was significantly increased in the MG patients ( RR =4.41, P <0.05) compared to the controls when DQB1*0302 and DQB1*0201 all had a higher frequency in patients. It had been shown that the alanine in position 57 (Ala57) of HLA DQ β polymorphic aminoteriminal domain is positively correlated to MG ( RR =5.1, P <0.005) and a stronger association was observed in the MG patients with thymomas ( RR =57.88, P <0.001). Conclusions HLA DQ β gene expressing Ala57 contributes to the susceptibility to MG in Chinese, especially in MG with thymoma. The substitution of neutral Ala by negatively charged Asp in position 57 of the HLA DQ β chain is the genetic susceptible basis of MG.