TNF-α启动子-308位点多态性与重症肌无力的相关性

Association of the tumor necrosis factor-alpha-308 polymorphism with myasthenia gravis

目的探讨肿瘤坏死因子(tumor necrosis factor,TNF)-α启动子区域-308位点基因多态性与重症肌无力(myasthenia gravis,MG)的相关性。方法采用聚合酶链反应及基因测序技术检测289例MG患者与304名健康对照者TNF-α-308位点的基因型及等位基因分布频率,进一步根据MG患者性别、年龄、临床分型等进行分组,比较各组间TNF-α-308位点基因型及等位基因分布频率的差异。结果 MG患者及健康对照组均未发现A/A基因型;MG患者TNF-α启动子-308位点G/A基因型和等位基因A出现的频率与健康对照组比较差异无统计学意义(P>0.05)。相同性别间比较,男性MG组G/A基因型(P=0.025,OR=2.673,95%CI:1.105～6.467)及A等位基因(P=0.029,OR=2.533,95%CI:1.071～5.991)出现的频率高于健康对照组;发病年龄<40岁的MG组,全身型G/A基因型(P=0.004,OR=4.760,95%CI:1.533～14.778)及A等位基因(P=0.005,OR=4.298,95%CI:1.450～12.740)出现的频率高于眼肌型。结论 TNF-α-308位点多态性与中国北方地区男性MG患者及早发全身型MG患者发病相关。

Objective To analyze the relationship between the single nucleotide polymorphisms （SNP） of the tumor necrosis factor-alpha -308 （TNF-α-308） and the myasthenia gravis （MG） in Han population from North of China. Methods TNF-α-308 gene polymorphism in 289 patients with MG and 304 healthy people was detected by polymerase chain reaction restriction fragment length polymorphism （PCR-RFLP） and DNA sequencing technology. Sub-groups were divided according to gender, age, and clinical classification. The genotypes of the different groups were statistically analyzed. Results In the MG group and control group, A/A genotype was not found, while TNF-α-308 G/G and G/A genotype were detected. There was no significant difference in the frequencies of TNF-α-308 G/A genotype and A allele between the MG group and the control group （P〉0.05）. The frequencies of TNF-α-308 G/A genotype and A allele were higher in the MG group [ （P =0. 025, OR=2. 673, 95%CI： 1. 105-6. 467）, （P=0. 029, OR=2. 533, 95%CI： 1. 071-5. 991）, respectively] than in the control group in the male population. In the patients younger than 40, the frequencies of TNF-a-308 G/A genotype and A allele were increased in the anti-oMG[ （P=0. 004, OR=4. 760, 95%CI： 1. 533-14. 778）, （P=0. 005, OR=4. 298, 95%CI： 1. 450-12. 740）, respectively] compared with oMG patients. A allele were not found in the late-onset anti-oMG patients. Conclusions TNF-α-308 G/A genotype and A allele may be associated with the early-onset anti-oMG patients and male MG patients from North of China.