STAT3和STAT4基因多态性与重症肌无力易感性的关系研究

Correlations of STAT3 and STAT4 gene polymorphisms with myasthenia gravis susceptibility

目的探讨信号传导和转录激活因子3(STAT3)基因位点rs744166、rs1053005及STAT4基因rs7574865位点多态性与重症肌无力(MG)易感性的关系。方法选择哈尔滨医科大学第二附属医院神经内科自2019年9月至2022年6月收治的149例MG患者作为MG组,另外选取医院同期的普通体检者148例作为对照组。采集所有受试者外周静脉血,采用多重高温连接酶检测反应技术(iMLDR)检测STAT3基因rs744166、rs1053005位点,STAT4基因rs7574865位点多态性,比较2组受试者,不同性别、年龄受试者,眼肌型MG和全身型MG患者,有胸腺瘤和无胸腺瘤MG患者,乙酰胆碱受体抗体(AchR-Ab)阳性和AChR-Ab阴性MG患者各基因位点多态性的差异。结果(1)与对照组比较,MG组STAT4基因rs7574865位点的GT、TT基因型频率增高(37.2%vs.57.0%;10.1%vs.11.4%),GG基因型频率降低(52.7%vs.31.5%),G等位基因频率降低(71.3%vs.60.1%),T等位基因频率(28.7%vs.39.9%)增高,差异均有统计学意义(P<0.05)。(2)与对照组男性受试者比较,MG组男性患者STAT4基因rs7574865位点的GT、TT基因型频率增高,GG基因型频率降低,G等位基因频率降低,T等位基因频率增高,差异均有统计学意义(P<0.05);与对照组女性受试者比较,MG组女性患者STAT4基因rs7574865位点GT、TT基因型频率增高,GG基因型频率降低,差异均有统计学意义(P<0.05)。与对照组中≤50岁受试者比较,MG组中≤50岁患者STAT4基因rs7574865位点的GT、TT基因型频率增高,GG基因型频率降低,G等位基因频率降低,T等位基因频率增高,差异均有统计学意义(P<0.05);与对照组中>50岁受试者比较,MG组中>50岁患者STAT4基因rs7574865位点GT基因型频率增高,GG、TT基因型频率降低,差异均有统计学意义(P<0.05)。(3)眼肌型和全身型MG患者、有胸腺瘤和无胸腺瘤MG患者、AChR-Ab阳性和AChR-Ab阴性患者各基因位点的基因型、等位基因频率的差异均无统计学意义(P>0.05)。结论MG易感性与STAT4基因rs7574865位点多态性有关,携带GT/TT基因型、T等位基因的≤50岁或男性人群易患MG。

ObjectiveTo investigate the correlations of myasthenia gravis(MG)susceptibility with STAT3(rs744166 and rs1053005)and STAT4(rs7574865)gene polymorphisms.MethodsA total of 149 MG patients admitted to Department of Neurology,Second Affiliated Hospital of Harbin Medical University from September 2019 to June 2022 were selected as MG group,and 148 subjects accepted physical examination in our hospital at the same period were selected as control group.Peripheral venous blood of all subjects was collected.Improved multiplex ligation detection reaction(imLDR)assay was used to detect the STAT3(rs744166 and rs1053005)and STAT4(rs7574865)gene polymorphisms.Differences in polymorphisms of various gene loci were compared between the MG group and control group,among subjects with different gender or age,between MG patients with and without thymoma,between AChR-Ab positive and AChR-Ab negative MG patients,and between patients with eye muscle MG and systemic MG.Results(1)Compared with the control group,the MG group had significantly increased GT and TT genotype and T allele frequencies(37.2%vs.57.0%;10.1%vs.11.4%;28.7%vs.39.9%),and decreased GG genotype and G allele frequencies(52.7%vs.31.5%;71.3%vs.60.1%)at rs7574865 locus in STAT4 gene(P<0.05).(2)Compared with male subjects in the control group,the male patients in MG group had significantly increased GT and TT genotype and T allele frequencies,and decreased GG genotype and G allele frequencies at rs7574865 locus in STAT4 gene(P<0.05);compared with female subjects in the control group,the female patients in MG group had significantly increased GT and TT genotype frequencies and decreased GG genotype frequency at rs7574865 locus in STAT4 gene(P<0.05).Compared with subjects≤50 years old in the control group,patients≤50 years old in the MG group had significantly increased GT and TT genotype and T allele frequencies,and decreased GG genotype and G allele frequencies at rs7574865 locus in STAT4 gene(P<0.05);compared with subjects>50 years old in the control group,patients>50 years old in the MG group had significantly increased GT genotype frequency and decreased GG and TT genotype frequencies at rs7574865 locus in STAT4 gene(P<0.05).(3)No significant differences in genotype and allele frequencies were noted between MG patients with and without thymoma,between AChR-Ab positive and AChR-Ab negative MG patients,or between patients with eye muscle MG and systemic MG(P>0.05).ConclusionMG susceptibility is associated with rs7574865 polymorphism of STAT4 gene;the male subjects or subjects≤50 years old with GT/TT genotype or T allele are susceptible to MG.