免疫调节相关基因多态性与重症肌无力的易感性研究OA
Investigation of susceptibility of myasthenia gravis to polymorphisms in immune regulation-related genes
目的:探讨重症肌无力(MG)易感性与免疫调节相关基因蛋白酪氨酸磷酸酶非受体型22(PTPN22)、肿瘤坏死因子诱导蛋白3(TNFAIP3)和TNFAIP3相互作用蛋白1(TNIP1)、干扰素调节因子5(IRF5)、T淋巴细胞免疫球蛋白黏蛋白3(Tim-3)、程序性细胞死亡蛋白1(PDCD1)多态性的相关性.方法:选取2019年9月至2022年6月在哈尔滨医科大学第二附属医院确诊的MG患者149例及148例健康志愿者为研究对象,采用改良多重高温连接酶检测反应技术(iMLDR)对PTPN22(rs2488457 C/G、rs33996649 C/T)、TNFAIP3 rs2230926 G/T和TNIP1 rs3792783 G/A、IRF5 rs10954213 G/A、Tim-3 rs10515746 C/A、PDCD1 rs11568821 C/T基因位点进行基因多态性分型.结果:PTPN22 rs2488457位点C等位基因频率MG组(38.6%)高于对照组(29.7%)(χ2=5.183,P=0.023);C等位基因频率在女性MG组(38.3%)高于对照组(27.6%)(χ2=4.008,P=0.045);C等位基因频率在早发型(≤50岁)MG组(43.7%)高于对照组(30.9%)(χ2=5.378,P=0.020);C等位基因频率在眼肌型MG组(47.3%)高于全身型MG组(33.3%);G等位基因频率在全身型MG组(66.7%)高于眼肌型MG组(52.7%)(χ2=5.772,P=0.016).TNFAIP3 rs2230926位点G等位基因频率MG组(7.0%)高于对照组(3.4%)(χ2=4.040,P=0.044).TNIP1 rs3792783位点GG、AA基因型频率在MG组为(14.8%,59.0%),高于对照组(14.2%,46.6%),差异有统计学意义(χ2=6.041,P=0.049).MG组与对照组其余位点基因型频率和等位基因频率差异无统计学意义(P>0.05).结论:MG 易感性与 PTPN22rs2488457、TNFAIP3rs2230926、TNIP1rs3792783多态性相关,而与PTPN22rs rs33996649、IRF5 rs10954213、Tim-3 rs10515746和PDCD1 rs11568821基因多态性无明显相关性.
Objective:To investigate correlation between susceptibility to myasthenia gravis(MG)and polymorphisms of im-mune regulation-related genes:Protein tyrosine phosphatase non-receptor 22(PTPN22),tumor necrosis factor alpha-induced protein 3(TNFAIP3),TNFAIP3-interacting protein 1(TNIP1),interferon regulatory factor 5(IRF5),T cell immunoglobulin domain and mu-cin domain-3(Tim-3),programmed cell death protein 1(PDCD1).Methods:Improved multiple ligase detection reaction technique(iMLDR)was utilized to identify SNP genotypes in 149 MG patients who were recruited in the Second Affiliated Hospital of Harbin Medical University from September 2019 to June 2022,and in 148 healthy blood donors,including PTPN22(rs2488457 C/G,rs33996649 C/T),TNFAIP3 rs2230926 G/T,TNIP1 rs3792783 G/A,IRF5 rs10954213 G/A,Tim-3 rs10515746 C/A,and PDCD1 rs11568821 C/T.Results:Frequency of C alleles at PTPN22 rs2488457 in MG group(38.6%)was significantly higher than healthy controls(29.7%)(χ2=5.183,P=0.023).Genetic frequency of C alleles(38.3%)in female MG group was higher than control group(27.6%)(χ2=4.008,P=0.045).Within early-onset MG group(≤50 years old),frequency of C alleles(43.7%)was higher than that in control group(30.9%)(χ2=5.378,P=0.020).There was a higher frequency of C alleles in ocular MG patients(47.3%)compared to generalized MG(33.3%),conversely,there was a higher frequency of G allele in generalized MG patients(66.7%)than in ocular MG patients(52.7%)(χ2=5.772,P=0.016).G alleles frequency for TNFAIP3 rs2230926 within MG group(7.0%)was also higher than healthy controls(3.4%)(χ2=4.040,P=0.044).Frequencies of GG and AA genotypes at TNIP1 rs3792783 locus were 14.8%and 59.0%in MG group,which were higher than those in control group(14.2%,46.6%)(χ²=6.041,P=0.049).However,no association observed in genotype frequencies and allele frequencies at remaining loci between MG and control groups(P>0.05).Conclusion:Associations have been observed between MG with PTPN22 rs2488457,TNFAIP3 rs2230926 and TNIP1rs3792783 SNPs,but not with PTPN22 rs33996649,IRF5 rs10954213,Tim-3 rs10515746 and PDCD1 rs11568821 SNPs.
邓慧;张小波;演员
内蒙古医科大学附属医院神经内科,呼和浩特 010050哈尔滨医科大学第二附属医院神经内科,哈尔滨 150001内蒙古医科大学附属医院神经内科,呼和浩特 010050
医药卫生
重症肌无力自身免疫病遗传变异单核苷酸多态性iMLDR
Myasthenia gravisAutoimmune diseasesGenetic variationSNPiMLDR
《中国免疫学杂志》 2026 (6)
1419-1426,8
内蒙古医科大学附属医院博士启动金(MYFY BS 202132)内蒙古自治区自然科学基金项目(2020MS08194).
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