ABSTRACT

TNF-α is an important cytokine of the inflammatory response involved in the pathogenesis of relapsing-remitting multiple sclerosis (RRMS). The aim of this study is to explore the association between the promoter polymorphism −308G/A in the TNF-α gene (rs1800629) with genetic susceptibility to RRMS.

Methods: A group of 183 RRMS patients and 169 age and gender-matched healthy controls were enrolled in the study. Genotyping of the polymorphism was performed by PCR-restriction fragment length polymorphism and quantification of TNF-α serum levels was conducted by ELISA.

Results: The genotype distribution in female patients showed a significantly elevated frequency of heterozygotes (AG) (23.5% vs. 12.8%, OR = 2.072, p = 0.029) in comparison with the healthy women. Substantially higher TNF-α serum levels were observed in females compared to males, in both patients and healthy controls (p < 0.05). According to the genotype, TNF-α levels in the RRMS group were calculated in the following order: for GA/AA genotypes (5.67pg/ml vs. 3.48pg/ml, p = 0.0031) and for GG genotypes (4.58pg/ml vs. 3.52pg/ml, p = 0.00043). Moreover, the carriers of at least one A-allele of −308G/A TNF-α polymorphism (GA+AA) are significantly associated with two fold increased risk for RRMS development (OR = 1.950; p = 0.042) in women in contrast to men as well as associated with early onset of the disease (OR = 2.400; p = 0.021).

Conclusion: Our study showed that the level of TNF-α in the serum of patients with RRMS showed a significant association with the −308G/A TNF-α polymorphism and gender dependency.

摘要

TNF-α 是炎症反应的重要细胞因子，参与复发缓解型多发性硬化症 (RRMS) 的发病机制。本研究的目的是探讨TNF-α基因 (rs1800629) 中启动子多态性 -308G/A与 RRMS 遗传易感性之间的关联。

方法：本研究招募了 183 名 RRMS 患者和 169 名年龄和性别匹配的健康对照。多态性的基因分型通过 PCR 限制性片段长度多态性进行，TNF-α 血清水平的定量通过 ELISA 进行。

结果：与健康女性相比，女性患者的基因型分布显示杂合子 (AG) 的频率显着升高（23.5% 对 12.8%，OR = 2.072，p = 0.029）。与男性相比，在患者和健康对照中，女性的 TNF-α 血清水平显着更高（p < 0.05）。根据基因型，RRMS 组的 TNF-α 水平按以下顺序计算：GA/AA 基因型（5.67pg/ml 与 3.48pg/ml，p = 0.0031）和 GG 基因型（4.58pg/ml与 3.52pg/ml，p = 0.00043）。此外，-308G/A TNF-α的至少一个A等位基因的携带者 与男性相比，多态性 (GA+AA) 与女性 RRMS 发展风险增加两倍（OR = 1.950；p = 0.042）显着相关，并且与疾病的早发相关（OR = 2.400；p = 0.021 ）。

结论：我们的研究表明，RRMS 患者血清中 TNF-α 水平与 -308G/A TNF-α多态性和性别依赖性显着相关。