Paediatric Rheumatology Unit, Department of Paediatrics, "G. d'Annunzio" University, Chieti-Pescara, Italy.
Laboratory of Molecular Genetics, Department of Psychological, Humanities and Territorial Sciences, "G. d'Annunzio" University, Chieti-Pescara, Italy.
Semin Arthritis Rheum. 2015 Aug;45(1):35-41. doi: 10.1016/j.semarthrit.2015.02.003. Epub 2015 Feb 19.
To investigate the genetic contribution of TNF-α gene polymorphisms on the disease course and therapeutic response in patients with juvenile idiopathic arthritis (JIA).
74 Caucasian patients with JIA were recruited with a control group of 77 healthy children. DNA was extracted for analysis of TNF-α gene promoter polymorphisms at positions -163, -244, -238, -376, and -308.
No SNPs at position -163 were observed, while we observed only SNPs at positions -244 and -376 in the controls. No differences were observed in the prevalence of SNPs at -238 and -308 between JIA and controls. In JIA patients no significant differences were observed between the -238 and -308 G/A genotypes and different disease phenotypes. We observed a significant lower disease activity expressed in the carriers of -308 GG genotype with respect to GA and AA genotypes after 6 (p = 0.008 and p = 0.013, respectively) and 12 months of disease (p = 0.02 and p = 0.08, respectively). Also the -238 GG genotypes showed a better disease course after 12 months of disease. Moreover, the -238/-308 GG genotypes presented the higher reduction of disease activity both after 6 (p < 0.01 vs GA and p < 0.01 vs AA) and 12 months from baseline (p < 0.01 vs GA and p < 0.01 vs AA). After 12 months of biologic therapy, a significant higher disease activity was observed in patients with genotype -308 AA respect to both GA (p = 0.012) and GG (p = 0.016).
JIA patients carrying the TNF-α -308 GA/AA and -238 GA genotypes are associated with a worse prognosis and with a lower response to anti-TNF-α drugs.
研究 TNF-α 基因多态性对幼年特发性关节炎（JIA）患者疾病过程和治疗反应的遗传贡献。
招募了 74 名白人 JIA 患者和 77 名健康儿童作为对照组。提取 DNA 用于分析 TNF-α 基因启动子在位置-163、-244、-238、-376 和-308 的多态性。
在对照组中仅观察到-244 和-376 位置的 SNP，而在-163 位置未观察到 SNP。JIA 和对照组之间-238 和-308 处 SNP 的患病率没有差异。在 JIA 患者中，-238 和-308 G/A 基因型与不同的疾病表型之间未观察到显著差异。我们观察到-308 GG 基因型的患者在 6 个月（p=0.008 和 p=0.013）和 12 个月（p=0.02 和 p=0.08）后疾病活性表达显著降低，与 GA 和 AA 基因型相比。此外，-238 GG 基因型在疾病 12 个月后表现出更好的疾病过程。此外，-238/-308 GG 基因型在 6 个月（p<0.01 与 GA 和 p<0.01 与 AA）和从基线开始 12 个月（p<0.01 与 GA 和 p<0.01 与 AA）后，疾病活性均有较高的降低。在接受生物治疗 12 个月后，基因型-308 AA 的患者与 GA（p=0.012）和 GG（p=0.016）相比，疾病活动度显著更高。
携带 TNF-α-308 GA/AA 和-238 GA 基因型的 JIA 患者预后较差，对 TNF-α 拮抗剂药物的反应较低。
