TNF-Alpha-308A Allele is Associated with the Presence of Tophi: A Preliminary Study

目的：研究痛風石的產生和甲型腫瘤壞死因子促進因子基因 –308 位置之G→A對偶基因多型性之相關性。 方法：收集門診77 位確定診斷為痛風之病人，依據痛風石的有無分成兩組；有痛風石的病人共37 人，沒有痛風石的病人共40 人。收集並分析臨床病史和實驗室血清學學報告，並使用PCR-RFLP 實驗方法研究甲型腫瘤壞死因子促進因子基因--308 位置之G→A對偶基因多型性情形。 結果：比較臨床病史和實驗室血清學學報告在兩組病人並無差異(p>0.05) 。甲型腫瘤壞死因子促進因子基因 –308 位置之異合子(G/A) 會加重痛風石的產生(p=0.015, odds ratio 6.11, 95% C.I. 1.22-30.49) 。甲型腫瘤壞死因子促進因子基因 –308 位置之A對偶基因在有痛風石這組病人的比例明顯多於沒有痛風石的病人(p=0.02, odds ratio 5.4, 95% C.I. 1.13-25.88) 。在兩組病人中帶有至少一個G對偶基因的比例都是100% 。而在有痛風石和沒有痛風石病人中，帶有一個A對偶基因的比例分別是12.2% 及2.5% (p=0.035, odds ratio 4.87, 95% C.I. 0.99-24.00) 。 結論：據我們所知，這是第一篇提出痛風石的產生和甲型腫瘤壞死因子促進因子基因 –308 位置之G→A基因多型性有相關的研究。未來仍然需要有更多關於甲型腫瘤壞死因子的其他位置多型性的探討，進一步瞭解痛風石產生的分子機轉。
Objective: To investigate the relationship between the presence of tophi and the TNF-alpha (TNFα) promoter –308G/A polymorphism in gouty patients. Methods: Thirty-seven gouty patients with any visible or palpable tophi on the four limbs joints were recruited as study subjects, and 40 gouty patients without visible or palpable tophi were recruited as controls. We collected and analyzed the clinical characteristics and laboratory data of patients in both groups. The TNFα –308G/A polymorphism was analyzed by PCR-RFLP methods. Results: There was no statistically significant difference in personal history, family history of gout or baseline laboratory data between patients with tophi and those without. There were statistically significant differences in favor of developing tophi in the heterozygote TNFα –308G/A (p=0.017, odds ratio 6.11, 95% C.I. 1.22-30.49). The frequency of the TNFα –308A allele was significantly higher in patients with tophi than in patients without (p=0.02, odds ratio 5.4, 95% C.I. 1.13-25.88). The –308 allele carriage of the G allele was 100% in both the tophi and non-tophi groups. In patients with tophi and without tophi, the –308 allele carriage of the A allele was 12.2% and 2.5%, respectively (p=0.035, odds ratio 4.87, 95% C.I. 0.99-24.00). Conclusion: To our knowledge, this is the first study to find that the TNFα –308A allele is associated with the presence of tophi in gouty patients. Further study of other polymorphisms in the TNF promoter is indicated to understand more about the tophi.