Published Online
on June 3, 2002

A more recent version of this article appeared on June 25, 2002

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Submitted on March 26, 2002
Revised on May 7, 2002
Accepted on May 7, 2002

Serotonin Transporter Gene Polymorphism and Myocardial Infarction. Etude Cas-Témoins de l'Infarctus du Myocarde (ECTIM)

Frédéric Fumeron PhD^*, Dina Betoulle MSc, Viviane Nicaud MA, Alun Evans MD, Frank Kee MD, Jean-Bernard Ruidavets MD, Dominique Arveiler MD, Gérald Luc MD, and François Cambien MD

From EA 3516 (F.F., D.B.), Faculté de Médecine Xavier Bichat, Paris, France; INSERM U525 (V.N., F.C.), Paris, France; MONICA Project (A.E., F.K.), Belfast, Northern Ireland, UK; MONICA Project (J.-B.R.), Haute-Garonne, Toulouse, France; MONICA Project (D.A.), Bas-Rhin, Strasbourg, France; and MONICA Project (G.L.), Lille, France.

Background—Depression is a risk factor for myocardial infarction (MI). Selective serotonin reuptake inhibitors reduce this risk. The site of action is the serotonin transporter (SLC6A4), which is expressed in brain and blood cells. A functional polymorphism in the promoter region of the SLC6A4 gene has been described. This polymorphism may be associated with the risk of MI.

Methods and Results—The SLC6A4 polymorphism has been investigated by polymerase chain reaction in 671 male patients with MI and in 688 controls from the Etude Cas-Témoins de l'Infarctus du Myocarde (ECTIM) multicentric study. Percentages for LL, LS, and SS genotypes were 35.5%, 45.4%, and 19.1%, respectively, for cases versus 28.1%, 49.1%, and 22.8%, respectively, for controls. S allele frequency was 41.8% and 47.4% for cases and controls, respectively. After adjustment for age and center by using multivariable logistic regression, the odds ratio for MI associated with the LL genotype was 1.40 (95% CI 1.11 to 1.76, P=0.0047).

Conclusions—The LL genotype of the SLC6A4 polymorphism is associated with a higher risk of MI. This could be attributable to the effect of the polymorphism on serotonin-mediated platelet activation or smooth muscle cell proliferation or on other risk factors, such as depression or response to stress.

Key words: serotonin transporter • genes • myocardial infarction • risk factors

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