Università del Piemonte Orientale A. Avogadro, DiSCAFF and Centro di Ricerca Interdipartimentale di Farmacogenetica e Farmacogenomica, Via Bovio 6, Novara, Italy.
Eur J Pharmacol. 2010 Sep 1;641(2-3):82-7. doi: 10.1016/j.ejphar.2010.04.049. Epub 2010 May 18.
The aim of the present observational study was to assess the value of the C825T polymorphism of the beta-3 subunit of G proteins (GNB3) as well as of variants in the SLC6A4 gene (5HTTLPR and STin2 VNTR) and DRD2 gene (TaqI A and NcoI) as predictive markers for consistency in headache response to triptans in migraine patients. Consistent responders to triptans were defined as the migraineurs who experienced a > or =2 point reduction in a 4-point scale intensity of pain from 3 (severe) to 0 (absent) 2h after triptan administration, in at least two attacks out of the three. Genotyping was performed by PCR and PCR-RFLP on genomic DNA extracted from peripheral blood. The impact of clinical and biological variables on consistency status of headache response to triptans was evaluated by using a binary logistic regression model with stepwise selection. Forty-three (33%) of the 130 migraine patients included in the study did not consistently respond to triptan administration. In a binary logistic regression model, STin 2.12/12 genotype (OR=3.363, 95% CI: 1.262-8.966, P=0.005) and non-use of migraine prophylactic medications (OR=2.848, 95% CI: 1.019-7.959, P=0.010) were found as significant factors increasing the odds of achieving inconsistent response to triptans. The analysis of classificatory power of the model showed moderate values of sensitivity (0.56), high specificity (0.87), and an overall prediction correctness (0.77). These results support the role of STin2 VNTR polymorphism of serotonin transporter gene as a relevant genetic factor conferring a higher risk of inconsistent response to triptans in migraine patients.
本观察性研究旨在评估 G 蛋白β-3 亚单位（GNB3）的 C825T 多态性、SLC6A4 基因（5HTTLPR 和 STin2VNTR）和 DRD2 基因（TaqIA 和 NcoI）的变异作为偏头痛患者对曲坦类药物头痛反应一致性的预测标志物的价值。一致的曲坦类药物反应者定义为在曲坦类药物给药后 2 小时内，从 3 分（严重）至 0 分（无）疼痛强度的 4 分制评分中疼痛至少减少 2 分，至少在 3 次发作中的 2 次中出现这种情况的偏头痛患者。通过聚合酶链反应（PCR）和聚合酶链反应-限制性片段长度多态性（PCR-RFLP），从外周血提取的基因组 DNA 上进行基因分型。使用逐步选择的二项逻辑回归模型评估临床和生物学变量对曲坦类药物头痛反应一致性状态的影响。在纳入的 130 例偏头痛患者中，有 43 例（33%）对曲坦类药物治疗不持续反应。在二项逻辑回归模型中，STin2.12/12 基因型（OR=3.363，95%CI：1.262-8.966，P=0.005）和不使用偏头痛预防性药物（OR=2.848，95%CI：1.019-7.959，P=0.010）被发现是增加曲坦类药物治疗不一致反应几率的显著因素。模型分类能力的分析显示，敏感性（0.56）、特异性（0.87）和总体预测正确性（0.77）的中等值。这些结果支持 5-羟色胺转运体基因 STin2VNTR 多态性作为一种相关遗传因素的作用，使偏头痛患者对曲坦类药物治疗的反应不一致的风险更高。
