Department of Neurology, University Hospital of Muenster, University of Muenster, Albert-Schweitzer-Strasse 33, 48149 Münster, Germany.
J Neural Transm (Vienna). 2010 Nov;117(11):1253-60. doi: 10.1007/s00702-010-0468-6. Epub 2010 Aug 26.
The serotonergic system plays a major role in the etiology of migraine. The rate-limiting enzyme in serotonin homeostasis and availability is tryptophan hydroxylase (TPH). The TPH2 isoform is responsible for the cerebral serotonin biosynthesis. To investigate the role of genetic variation in TPH2 in the pathogenesis of migraine eight haplotype tagging SNPs covering the whole TPH2 gene where chosen using Haploview and genotyped in 503 migraineurs and 515 healthy controls. Association analysis was performed on a single SNP and haplotype basis using χ² and logistic regression analysis. Single SNP analysis revealed a weak association with migraine, which did not remain after correction for multiple testing. Haplotype analyses revealed association of a haplotype with migraine without aura. Stratification by aura and triptan response did not reveal a positive association with the investigated polymorphisms. These results suggest a possible influence of genetic variation in TPH2 in the pathogenesis of migraine.
5-羟色胺能系统在偏头痛的发病机制中起主要作用。色氨酸羟化酶（TPH）是 5-羟色胺内稳态和可用性的限速酶。TPH2 同工型负责脑内 5-羟色胺的生物合成。为了研究 TPH2 基因多态性在偏头痛发病机制中的作用，我们使用 Haploview 选择了覆盖整个 TPH2 基因的 8 个单倍型标签 SNP，并对 503 例偏头痛患者和 515 例健康对照者进行了基因分型。采用 χ² 和逻辑回归分析，在单 SNP 和单倍型基础上进行关联分析。单 SNP 分析显示与偏头痛有弱关联，但经多次检验校正后，这种关联不再存在。单倍型分析显示，一种无先兆偏头痛的单倍型与偏头痛相关。对先兆和曲坦类药物反应进行分层分析后，未发现与所研究的多态性有阳性关联。这些结果提示 TPH2 基因多态性可能影响偏头痛的发病机制。
