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A Polymorphism in the Serotonin Transporter Gene Regulatory Region and Frequency of Migraine Attacks


Address all correspondence to Kazuhiko Kotani, MD, Department of Clinical Laboratory Medicine, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago 683-8503, Japan.


Background.—The serotonergic system has been thought to play an important part in the pathophysiology of migraine.

Objective.—To study an association between the polymorphism of serotonin (5-hydroxytryptamine [5-HT]) transporter gene-linked polymorphic region (5-HTTLPR) and migraine.

Method.—We compared 151 patients with migraine with 190 healthy unrelated control subjects. The 5-HTTLPR polymorphism was detected using polymerase chain reaction. Migraine patients were interviewed regarding attack frequency in the last 6 months.

Results.—We denoted the products of the 484-base pair (bp) fragments as the short (s) and those of 528 bp as the long (l) allele according to the previously reported manner. Migraine patients with s/s genotype were compared with those with l/s and l/l genotype. We did not find significant differences in the genotype and allele frequencies of 5-HTTLPR between patients with migraine and control subjects. Among patients with migraine, those with s/s type had significantly more frequent attacks than those with the l/s or l/l type.

Conclusions.—This polymorphism does not appear to be involved in a genetic predisposition to the disease but may affect the frequency of attacks in patients with migraine. These findings may contribute to our understanding of factors that influence the clinical severity of migraine.