类风湿性关节炎患者TNF基因多态性表达及意义的初步探讨

A Study on TNF-α Gene Polymorphism in RA Patients and its Singificance

目的 探讨肿瘤坏死因子 (TNF) -α基因多态性与类风湿性关节炎 (RA)的相关性。方法 采用等位基因特异引物多聚酶链反应 (PCR)方法对 3 4例RA患者与 3 5例对照组的TNFα -3 0 8位基因进行TNF1 和TNF2 基因型检测 ,并采用ELISA法检测其血清中TNFα的含量。结果 RA患者TNF2 的基因型分布以TNF2 为主 ( 5 2 9%) ,正常对照组的基因型分布以TNF1 为主 ( 68 6%) ,两者有显著性差异 ( χ2 =2 7 71,P <0 0 1)。RA患者血清中TNFα含量明显高于正常对照组 (P <0 0 1) ,不同TNF基因表型的RA患者血清中TNFα含量有显著性差异 (F =3 2 60 ,P <0 0 1) ,TNF2 及杂合型基因表型RA患者血清中TNFα含量明显高于TNF1 者。结论 TNFα -3 0 8的基因多态性直接影响着TNF分泌 。

Objective To investigate the relationship between tumor necrosis factor-α(TNF-α) gene polymorphism and rheumatoid arthritis (RA). Methods Genomic DNA from 34 RA patients and 35 ethnically matched controls were typed for TNF-α(308) gene polymorphism by allele-specific polymerase chain reaction(AS-PCR). The concentration of their serum TNF-α was measured by ELISA. Results The TNF genotypes in RA patients were respectively TNF 1 homozygote 14 7%, TNF 2 homozygote 52 9%, and TNF 1 and TNF 2 heterozygote 32 4%. TNF genotypes in controls were respectively TNF 1 homozygote 68 6%, TNF 2 homozygote 2 8%, and TNF 1 and TNF 2 heterozygote 28 6%. The significant difference was found in the distribution of TNF-α(308) genotype between the two groups (χ 2=27 71,P<0 01). The concentration of the serum TNF-α in RA patients was higher than that in controls(P<0 01). And the serum TNF-α concentrations of TNF 2/2 and TNF 2/1 genotypes were higher than those of TNF 1/1 genotype in RA patients (P<0 01). Conclusion TNF production in RA patients was influenced by TNF gene polymorphism, which suggested that TNF-α gene polymorphism may play a role in the pathogenesis of RA.