American Heart Journal
Volume 150, Issue 4 , Pages 652-658, October 2005

Influence of serotonin transporter gene polymorphism on depressive symptoms and new cardiac events after acute myocardial infarction

  • Daisaku Nakatani, MD

      Affiliations

    • Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan
  • ,
  • Hiroshi Sato, MD, PhD

      Affiliations

    • Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan
    • Corresponding Author InformationReprint requests: Hiroshi Sato, MD, PhD, Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
  • ,
  • Yasuhiko Sakata, MD, PhD

      Affiliations

    • Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan
  • ,
  • Issei Shiotani, MD, PhD

      Affiliations

    • Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan
  • ,
  • Kunihiro Kinjo, MD, PhD

      Affiliations

    • Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan
  • ,
  • Hiroya Mizuno, MD

      Affiliations

    • Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan
  • ,
  • Masahiko Shimizu, MD

      Affiliations

    • Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan
  • ,
  • Hiroshi Ito, MD, PhD

      Affiliations

    • Sakurabashi Watanabe Hospital, Osaka, Japan
  • ,
  • Yukihiro Koretsune, MD, PhD

      Affiliations

    • Osaka National Hospital, Osaka, Japan
  • ,
  • Atsushi Hirayama, MD, PhD

      Affiliations

    • Osaka Police Hospital, Osaka, Japan
  • ,
  • Masatsugu Hori, MD, PhD

      Affiliations

    • Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan
  • ,
  • on behalf of the Osaka Acute Coronary Insufficiency Study (OACIS) Group

Received 30 August 2004; accepted 15 March 2005.

This work was supported by a grant-in-aid for University and Society Collaboration (15590743) from the Japanese Ministry of Education, Culture, Sports, Science, and Technology (Tokyo, Japan) and by a research grant from the Japan Arteriosclerosis Prevention Fund.

Background

In patients with acute myocardial infarction (AMI), depressive symptoms increase the risk for cardiac events. Recently, the S allele of the serotonin transporter (5-HTT) gene–linked polymorphic region was shown to reduce transcription of this gene and thus reduce serotonin reuptake, and this allele is linked with depressive symptoms as well as other psychiatric diseases. However, the influence of the S allele on depressive symptoms and cardiac events after AMI is unclear.

Methods

To investigate whether the S allele was associated with depressive symptoms and cardiac events after AMI, we prospectively examined depressive symptoms and new cardiac events in 2509 genotyped patients with AMI.

Results

Depressive symptoms were more common in patients with the S allele than in those without it (48.3% vs 35.0%, P = .02). Multivariate analysis revealed that the S allele was independently associated with depressive symptoms (odds ratio 2.19, 95% confidence interval [CI] 1.21-3.98, P = .01). Cardiac events (cardiac death, revascularization, heart failure, reinfarction, arrhythmia, and unstable angina) were more frequent in patients with the S allele than in those without it (31.3% vs 22.3%, P = .046). Multivariate Cox regression analysis revealed an association between the S allele and an increased risk for cardiac events (hazard ratio [HR] 1.69, 95% CI 1.03-2.78, P = .04). However, the HR became insignificant after an adjustment for depressive symptoms (HR 1.30, 95% CI 0.84-2.01, P = .24).

Conclusions

The S allele in the 5-HTT gene–linked polymorphic region is associated with an increased risk for subsequent cardiac events, which is mediated, at least in part, by the depressive symptoms in patients after AMI.

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PII: S0002-8703(05)00450-3

doi:10.1016/j.ahj.2005.03.062

American Heart Journal
Volume 150, Issue 4 , Pages 652-658, October 2005