Università del Piemonte Orientale A. Avogadro, DiSCAFF and Centro di Ricerca Interdipartimentale di Farmacogenetica e Farmacogenomica (CRIFF), Via Bovio, 6, 28100 Novara, Italy.
Eur J Neurol. 2012 Jan;19(1):69-75. doi: 10.1111/j.1468-1331.2011.03436.x. Epub 2011 May 18.
To evaluate the role of 5-HTTLPR, STin2 VNTR, and rs1042173T>G polymorphisms of the serotonin transporter gene (SLC6A4) as susceptibility factors for medication overuse headache (MOH) and to assess their value as predictors of the number of headache days per month, a potential marker of disease severity.
Genotyping was performed by PCR and PCR-RFLP on genomic DNA extracted from peripheral blood of 227 MOH patients and 312 control subjects. Logistic regression analysis was used to evaluate the association between the SL6A4 gene polymorphisms and MOH risk. The association between polymorphic variants and monthly headache days was evaluated by linear regression analysis.
Logistic regression analysis, adjusted for age and gender, revealed a nominal association between rs1042173T>G and MOH risk (TT vs. TG + GG, OR: 1.58 95% CI: 1.05-2.37, P = 0.028). In the linear regression analysis adjusted for age, gender, primary headache diagnosis, acute drug overused and monthly drug number, STin2 VNTR was found nominally associated with monthly headache days (12/12 vs. others, difference: 1.55 days, 95% CI: 0.01-3.08, P = 0.050). When STin2 VNTR and rs1042173T>G were analyzed in haplotypic combination, a global haplotype association emerged with monthly headache days which remained significant after Bonferroni correction for multiple comparisons (global haplotype association P = 0.0056).
Although a minor contribution of SLC6A4 variants in the genetic liability of MOH cannot be excluded, haplotype-based analysis of STin2 VNTR and rs1042173T>G polymorphisms allowed to identify a subgroup of MOH patients with a higher number of monthly headache and, possibly, with a more severe disease.
评估 5-羟色胺转运体基因（SLC6A4）的 5-HTTLPR、STin2 VNTR 和 rs1042173T>G 多态性作为药物过度使用性头痛（MOH）易感性因素的作用，并评估它们作为每月头痛天数的预测因子的价值，这是疾病严重程度的潜在标志物。
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）对 227 例 MOH 患者和 312 例对照的外周血基因组 DNA 进行基因分型。使用逻辑回归分析评估 SLC6A4 基因多态性与 MOH 风险之间的关联。通过线性回归分析评估多态性变异与每月头痛天数之间的关系。
调整年龄和性别后，逻辑回归分析显示 rs1042173T>G 与 MOH 风险之间存在名义关联（TT 与 TG+GG，OR：1.58，95%CI：1.05-2.37，P=0.028）。在调整年龄、性别、原发性头痛诊断、急性药物过度使用和每月药物数量的线性回归分析中，STin2 VNTR 与每月头痛天数呈名义相关（12/12 与其他，差异：1.55 天，95%CI：0.01-3.08，P=0.050）。当 STin2 VNTR 和 rs1042173T>G 进行单倍型组合分析时，与每月头痛天数相关的整体单倍型关联在经过多次比较的 Bonferroni 校正后仍然显著（全局单倍型关联 P=0.0056）。
尽管不能排除 SLC6A4 变异在 MOH 遗传易感性中的微小贡献，但 STin2 VNTR 和 rs1042173T>G 多态性的基于单倍型分析可以确定一个具有更高每月头痛天数的 MOH 患者亚组，并且可能具有更严重的疾病。
