江浙沪地区汉人HLA－DQA1基因对重症肌无力的遗传易感性研究

采用一种新的多聚酶链反应－限制性片段长度多态性（ＰＣＲ－ＲＦＬＰ）基因分型法，研究了江浙沪地区中国汉人重症肌无力（ｍｙａｓｔｈｅｎｉａｇｒａｖｉｓ，ＭＧ）４５例和对照组９８例的ＨＬＡ－ＤＱＡ１等位基因。发现ＭＧ的胸腺瘤型和非胸腺瘤型ＤＱＡ１基因遗传背景有所不同，ＨＬＡ－ＤＱＡ１＊０３０１基因参与非胸腺瘤型ＭＧ（尤其是男性组）的遗传易感作用（ＲＲ＝３．６３，Ｐ＜０．０５），家系分析支持群体研究结果。推测了中国汉人ＭＧ可能的ＨＬＡ易感单体型：ＤＱＡ１＊０３０１ＤＱＢ１＊０３０３－ＤＲＢ１＊０９０１和ＤＱＡ１＊０３０１－ＤＱＢ１＊０３０３－ＤＲＢ１＊０４０６．结果从基因分型的角度统一了关于华人ＭＧ与ＨＬＡ相关抗原提法不一致的报道，并揭示了ＭＧ的其它ＨＬＡⅡ系统易感基因ＤＱＢ１＊０３０１、ＤＲＢ１＊０９０１及ＤＲＢ１＊０４０６或ＤＢＲ＊０４０５存在的极大可能性。为进一步分析ＭＧ的遗传易感机理提供了重要依据。

RESRARCH ON THE GENETIC SUSCEPTIBILITY FOR MYASTHENIA GRAVIS IN CHINESE HANS BY GENOTYPING OF HLA-DQA1 WITH PCR-RFLP

Forty-five patients and 2 families with myasthenia gravis(MG)in Chinese Hans from Shanghai and its nearby regions and 98 controls were investigated for HLA genotyping by digesting the locus specific PCR amplified products with allele specific restriction enzymes:Apall,Bsajl,Fokl,Hphl,Mboll and Mnll.DQA1*0301 allele was significantly increased in MG without thymoma(NT-MG)especially in man group compared to healthy controls and MG with thymoma(T-MG)(RR=3.63,P<0.05),but no single allele of DQA1 was associated with T-MG.We concluded that MG with thymoma and MG without thymolna are genetically different subgroups,and DQA1*0301 contributes to the genetic susceptibility of MG without thymoma-which was also confirmed by pedigree analysis.Based on this result,the linkage disequilibrium and the phenotyping data for Chinese reported,the susceptibility haplotypes for NT-MG were deduced as follows:(a)DQA1*0301-DQB*0303-DR81*0901,and(b)DQA1*0301-DQB1*0303-DRB1*0406 or *0405.These haplotypes are partly similar to those reported on Chinese Singaporean but quite different from those of Caucasoid data.