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多巴胺-β-羟化酶 19 位 bp 插入/缺失多态性影响慢性偏头痛患者的药物过度使用。

Dopamine-beta-hydroxylase 19-bp insertion/deletion polymorphism affects medication overuse in patients with chronic migraine.

机构信息

Headache and Pain Unit, Department of Neurological, Motor and Sensorial Sciences, IRCCS San Raffaele Pisana, Rome, Italy.

Biobanca InterIstituzionale Multidisciplinare, IRCCS San Raffaele Pisana, Rome, Italy.

出版信息

Neurol Sci. 2019 Aug;40(8):1717-1724. doi: 10.1007/s10072-019-03865-9. Epub 2019 Apr 10.

Abstract

Dopamine-beta-hydroxylase (DBH) enzyme activity is modulated at the genetic level by the presence of several polymorphisms. Among these, the 19-bp insertion/deletion (I/D) polymorphism (rs72393728/rs141116007) was investigated in several genetic association studies for its correlation with the susceptibility to develop episodic migraine, but conflicting results were achieved. In the present study we analyzed this genetic variant in a carefully characterized population of migraineurs encompassing both episodic and chronic migraine (with and without medication overuse) with the aim to perform a replication study and verify any possible correlation with migraine endophenotypes. Genotyping of the DBH 19-bp I/D polymorphism was performed on 400 migraine patients and 204 healthy individuals. The associations between genotypic frequencies and the clinical and sociodemographic features of migraineurs were then investigated. The DBH 19-bp I/D polymorphism did not correlate with migraine susceptibility or most clinical variables, with the exception of a statistically significant correlation within the subgroup of patients affected by chronic migraine were the individuals carrying the deleted (D) allele were significantly more prone to abuse in analgesics. As a result of this finding, the DBH 19-bp I/D polymorphism does not influence migraine susceptibility, but it might contribute to the development of medication overuse in patient with chronic migraine.

摘要

多巴胺-β-羟化酶(DBH)酶活性在遗传水平上受到几个多态性的调节。其中,19 个碱基插入/缺失(I/D)多态性(rs72393728/rs141116007)在几项遗传关联研究中被研究其与发作性偏头痛易感性的相关性,但结果存在冲突。在本研究中,我们在一个精心表征的偏头痛患者群体中分析了这种遗传变异,该群体包括发作性和慢性偏头痛(伴有和不伴有药物滥用),目的是进行复制研究并验证其与偏头痛内表型的任何可能相关性。对 400 名偏头痛患者和 204 名健康个体进行了 DBH 19-bp I/D 多态性的基因分型。然后研究了基因型频率与偏头痛患者的临床和社会人口统计学特征之间的关联。DBH 19-bp I/D 多态性与偏头痛易感性或大多数临床变量无关,除了在慢性偏头痛患者亚组中存在统计学意义的相关性,携带缺失(D)等位基因的个体明显更容易滥用镇痛药。由于这一发现,DBH 19-bp I/D 多态性不会影响偏头痛的易感性,但它可能有助于慢性偏头痛患者药物滥用的发展。

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