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Association between major depressive disorder and a functional polymorphism of the 5-hydroxytryptamine (serotonin) transporter gene: a meta-analysis

Kiyohara, Chikakoa; Yoshimasu, Kouichib

doi: 10.1097/YPG.0b013e328335112b
Review Article

Objectives A functional polymorphism in the promoter region of the 5-hydroxytryptamine (serotonin) transporter (5-HTT) gene, termed 5-HTTLPR, alters transcription of the 5-HTT gene. The short variation (S allele) produces less transcriptional efficiency of serotonin, which can partly account for psychiatric disorders. Despite strong biological plausibility, the relationship between 5-HTTLPR and the risk of major depressive disorder (MDD) is unclear. To elucidate the relationship, we applied meta-analysis techniques to molecular studies of 5-HTTLPR and MDD.

Methods A total of 22 articles were identified from MEDLINE through March 2008, using the search keywords ‘depression,’ ‘5-HTTLPR’, and ‘polymorphism.’ The authors assessed the evidence of genotypic association using STATA Version 8.2.

Results Summary frequencies of the S allele of 5-HTTLPR among Caucasians and Asians based on the random effects model were 42.1% [95% confidence interval (CI) = 40.5–43.6] and 76.8% (95% CI = 73.9–79.7), respectively. The distribution of the S allele was significantly different between Asians and Caucasians (P<0.001). The SS genotype was significantly associated with an increased risk of MDD among Caucasian populations (odds ratio = 1.41, 95% CI = 1.15–1.72), although there was no significant association among Asians.

Conclusion Although the summary risk for developing MDD in individuals with the ‘at-risk’ SS genotype of 5-HTTLPR may be small, MDD is such a common disease that even a small increase in risk translates to a large number of excess MDD cases in the population. Thus, 5-HTT may be a candidate MDD susceptibility gene.

aDepartment of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka

bDepartment of Hygiene, School of Medicine, Wakayama Medical University, Wakayama, Japan

Correspondence to Dr Chikako Kiyohara, PhD, Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, Japan

Tel: +81 92 642 6112; fax: +81 92 642 6115;


This work was presented in part at the 78th Annual Meeting of the Japanese Society for Hygiene, April 2008, Kumamoto.

Received 12 August 2008 Revised 8 June 2009 Accepted 27 June 2009

© 2010 Lippincott Williams & Wilkins, Inc.