Abstract:
The aim of the present study was to investigate the impact of CCR5 Δ32 and CTLA-4 polymorphisms on the response to IFN-β treatment in our cohort of MS patients from Croatia and Slovenia. Genomic DNA was obtained from 295 MS patients (230 female; 65 male) classified as responders (n = 173) and non-responders (n = 122) based on clinical criteria for treatment efficacy. Genotyping was performed via PCR/PCR-RFLP. No significant differences in the genotype/allele frequencies of CCR5Δ32 and CTLA-4 +49 A/G were detected between male responders and non-responders. A significantly higher prevalence (p = 0.039) of the CTLA-4 +49 AA genotype was found in female responders (42.1%) compared to non-responders (28.9%). Using multiple forward regression analysis, the CTLA-4 +49 AA genotype significantly predicted a positive response to IFN-β therapy in females (p = 0.011) and contributed to 4.5% of response variability. Furthermore, the combined presence of the CCR5Δ32 wtwt/CTLA-4 +49 AA genotype significantly predicted a positive response to treatment in females (p = 0.025). The age at disease onset, pretreatment relapse rate, and baseline EDSS score were not reliable predictors of treatment response in MS patients. Our results indicate that the presence of the CCR5Δ32 polymorphism was not associated with the response to IFN-β treatment, whereas the CTLA-4 +49 polymorphism showed a positive correlation with an optimal response in female patients.
摘要:
本研究的目的是研究CCR5Δ32和CTLA-4多态性对我们来自克罗地亚和斯洛文尼亚的MS患者队列中IFN-β治疗反应的影响。基因组DNA从295名MS患者(230名女性;65名男性)获得,基于治疗功效的临床标准将其分类为应答者(n=173)和非应答者(n=122)。通过PCR/PCR-RFLP进行基因分型。在男性应答者和非应答者之间未检测到CCR5Δ32和CTLA-449A/G的基因型/等位基因频率的显着差异。与无反应者(28.9%)相比,女性反应者(42.1%)中CTLA-449AA基因型的患病率(p=0.039)明显更高。使用多元前向回归分析,CTLA-4+49AA基因型显著预测女性对IFN-β治疗的阳性反应(p=0.011),并导致4.5%的反应变异性.此外,CCR5Δ32wtwt/CTLA-449AA基因型的联合存在显着预测了女性对治疗的阳性反应(p=0.025)。发病年龄,治疗前复发率,和基线EDSS评分不是MS患者治疗反应的可靠预测因子。我们的结果表明,CCR5Δ32多态性的存在与IFN-β治疗的反应无关,而CTLA-4+49多态性与女性患者的最佳反应呈正相关。