Università del Piemonte Orientale A. Avogadro, DiSCAFF and Centro di Ricerca Interdipartimentale di Farmacogenetica e Farmacogenomica (CRIFF), Novara, Italy.
Headache. 2010 Nov;50(10):1587-96. doi: 10.1111/j.1526-4610.2010.01757.x. Epub 2010 Aug 27.
The aim of the present study was to evaluate a possible involvement of 2 polymorphisms of the serotonin 5HT2A receptor gene (A-1438G and C516T) as risk factors for medication overuse headache (MOH) and whether the presence of these polymorphic variants might determine differences within MOH patients in monthly drug consumption.
Despite a growing scientific interest in the mechanisms underlying the pathophysiology of MOH, few studies have focused on the role of genetics in the development of the disease, as well as on the genetic determinants of the inter-individual variability in the number of drug doses taken per month.
Our study was performed by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism on genomic DNA extracted from peripheral blood of 227 MOH patients and 312 control subjects. Genotype-specific risks were estimated as odds ratios with associated 95% confidence intervals by unconditional logistic regression and adjusted for age and gender. A stepwise multiple linear regression analysis was employed to identify significant predictors of the number of drug doses taken per month.
No significant association was found between 5HT2A A and 1438G and C516T gene polymorphisms and MOH risk. In contrast, a higher consumption of monthly drug doses was observed among 516T 5HT2A carriers (median 50, range 13-120) compared to 516CC patients (median 30, range 12-128) (Mann-Whitney U-test, P = .018). In the stepwise multiple regression analysis, C516T 5HT2A polymorphism (P = .018) and class of overused drug (P = .047) emerged as significant, independent predictors of the monthly drug consumption in MOH patients.
Although our results do not support a major role of the A-1438G and C516T polymorphic variants of the 5HT2A gene in the susceptibility of MOH, our findings support an influence of the C516T polymorphism on the number of symptomatic drug doses taken and, possibly, on the drug-seeking behavior in these patients.
本研究旨在评估 5-羟色胺 5HT2A 受体基因（A-1438G 和 C516T）的 2 种多态性是否可能成为药物过度使用性头痛（MOH）的危险因素，以及这些多态性变体的存在是否可能导致 MOH 患者每月药物消耗的差异。
尽管人们对 MOH 病理生理学机制的研究兴趣日益浓厚，但很少有研究关注遗传学在疾病发展中的作用，以及个体间每月药物剂量差异的遗传决定因素。
我们通过聚合酶链反应（PCR）和聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法，对从 227 名 MOH 患者和 312 名对照者外周血中提取的基因组 DNA 进行了研究。通过非条件逻辑回归估计了特定基因型的风险比，并调整了年龄和性别。采用逐步多元线性回归分析，确定了每月药物剂量的显著预测因子。
5HT2A A 和 1438G 及 C516T 基因多态性与 MOH 风险之间未发现显著相关性。相反，与 516CC 患者（中位数 30，范围 12-128）相比，516T 5HT2A 携带者（中位数 50，范围 13-120）每月药物剂量消耗更高（Mann-Whitney U 检验，P =.018）。在逐步多元回归分析中，5HT2A C516T 多态性（P =.018）和过度使用药物类别（P =.047）是 MOH 患者每月药物消耗的显著独立预测因子。
尽管我们的结果不支持 5HT2A 基因的 A-1438G 和 C516T 多态性在 MOH 易感性中的主要作用，但我们的研究结果支持 C516T 多态性对症状性药物剂量的影响，以及可能对这些患者的药物寻求行为的影响。
