Polymorphism in the promoter of the gene for the serotonin transporter affects the age of onset of major depressive disorder in the Japanese population

Abstract

Objective: Recent research has suggested that a functional polymorphism in the promoter region of the serotonin transporter gene (serotonin transporter-linked polymorphic region, 5HTTLPR) may be implicated in gene-environment interactions leading to major depressive disorder (MDD).

Methods: Our study examined the association between 5HTTLPR and clinical variables of MDD in the Japanese population. We genotyped 5HTTLPR in 216 patients with MDD and 213 age- and sex-matched controls.

Results: The genotype distributions and allele frequencies were similar in the patients and controls. When the relationships between the polymorphism and several clinical variables (i.e., age of onset, number of episodes, presence of psychotic features, suicidal behavior, and family history) were examined, the dose of the long (l) allele had significant effects on the age of onset.

Conclusion: These results suggest that 5HTTLPR may not be entirely related to the development of MDD but may be related to the age of onset of MDD, which may be due to gene-environment interactions in the Japanese population.

Limitations: Because of the low frequencies of psychotic features and suicidal behavior, our results must be treated with caution until they are replicated in larger numbers of Japanese samples. MDD patients did not undergo a structured interview. Clinical information from the medical records may have not been complete.

Keywords: Age of onset; Gene association; Major depressive disorder; Promoter; Serotonin transporter.