重症肌无力患者HLA-B易感基因研究

Association between HLA-B and myasthenia gravis

目的探讨中国汉族重症肌无力(MG)患者及其不同亚型与人类白细胞抗原(HLA)-B等位基因的相关性。方法应用聚合酶链反应-序列特异性的寡核苷酸探针杂交法(PCR-SSOP)对91例中国汉族MG患者及171名健康对照者进行HLA-B等位基因分型,并采用病例-对照研究及显性遗传模式的方法系统分析HLA-B等位基因与MG患者不同临床亚型之间的相关性。结果按照性别、年龄、临床类型、抗乙酰胆碱受体(AChR)抗体及胸腺病变将患者组分为不同亚型后,结果显示HLA-B*46阳性率在男性、眼肌型、抗AChR抗体阴性及伴发胸腺瘤组中升高,HLA-B*08阳性率在早发型及全身型患者组中升高。与对照组比较,患者组HLA-B*35和B*38阳性率降低。结论 HLA-B*46基因可能是男性、眼肌型、抗AChR抗体阴性及伴发胸腺瘤的MG患者的易感基因或与易感基因相连锁;HLA-B*08可能是早发型及全身型MG患者的易感基因或与易感基因相连锁。HLA-B*35和B*38可能是MG的保护基因或与保护基因相连锁。

Objective To investigate the association between HLA-B alleles and myasthenia gravis （MG）, and its different subtypes, in Chinese Han patients. Methods A polymerase chain reaction method with sequence-specific oligonucleotide probe hybridization （PCR-SSOP） was used to determine the HLA-B genotype in 91 MG patients and 171 age- and sex-matched healthy controls. Based on the dominant inheritance pattern, the data were analyzed by a method of case-control study to find out the association between the HLA allele profile and different MG subtypes. Results It was found that HLA-B＊ 46 allele was more prevalent among MG patients than healthy controls in the male group （28.13% vs. 9.23 %, 0R=3.85, P〈0.05）, the ocular MG group （32.35 % vs. 9.36 %, OR= 4.63, P〈0.01）, the aeetylcholine receptor （AChR） antibody seronegative group （30.00% vs. 9.36%, OR=4.15, P%0.01）, and those with thymoma （28.57% vs. 9.36%, OR=3.88, P〈 0.05）. While HI.A-B~ 08 was more prevalent among the early-onset group （9.62% vs. 2.34%, OR：4.44, P d0.05）, and the generalized MG group （8.77% vs. 2.34%, OR：4.01, P%0.05）. Among MG patients, the prevalence of theHLA-B＊35 （2.2% vs. 11.11%,OR=0.18, P〈0.05） and B ＊ 38 alleles （1.1% vs. 7.02%, OR=0. 15, P%0.05） were decreased. Conclusions The results show that HLA-B＊ 46 might be positively associated with male sex, the ocular MG, the seronegative for acetylcholine receptor （AChR） antibody and the presence of thymoma. While HLA-B ＊ 08 might be positively associated with early-onset and the generalized MG. HLA-B ＊35 and B ＊38 were negatively associated with MG and they might be the protective genes or linking to protective genes of MG.