title: 5-Hydroxytryptamine 5-HT2A receptor and 5-hydroxytryptamine transporter polymorphisms in acute myocardial infarction.
abstract: This study was designed to analyse possible associations between DNA polymorphisms in the 5-hydroxytryptamine (5-HT; serotonin) 5-HT(2A) receptor and the 5-HT transporter (5-HTT) genes, and myocardial infarction (MI). 5-HT has been shown to be involved in cardiovascular pathophysiology. In addition to platelet aggregation and vascular contraction, 5-HT induces hyperplasia of artery smooth muscle cells. Recently, a 5-HT transporter gene polymorphism has been associated with MI. To determine the influence of genetic variation at the 5-HT(2A) receptor (T102C polymorphism) and the 5-HTT (insertion/deletion polymorphism) on the risk of developing early MI, we genotyped 210 MI patients of < 55 years old and 238 healthy control subjects for DNA polymorphisms in these genes. In addition, we genotyped 95 patients with late-onset MI (> 60 years old) to analyse the effects of these polymorphisms on the age at which the first MI episode occurred. The 5-HT(2A) receptor polymorphism was not associated with MI in our population. In addition, since the 5-HT(2A) receptor gene and genotype frequencies did not differ between patients with early and late onset of MI, this polymorphism does not appear to have an effect on age at the first MI episode. Gene and genotype frequencies for the 5-HTT promoter did not differ between patients < 55 years old and healthy controls (independent of smoking status). However, homozygotes for the deletion (the ss genotype, where s denotes the short allele) were present at a significantly higher frequency in patients >60 years old compared with patients < 55 years old (P = 0.009; P = 0.004 when only smokers were compared). According to our data, the ss genotype would seem to have a protective role against MI, delaying the age of onset of the first episode, especially among smokers. This could be a consequence of the lower 5-HTT levels linked to the s allele, so that individuals homozygous for the ss genotype may have lower 5-HT re-uptake by platelets.
authors.affiliation: Genética Molecular-Instituto Investigación Nefrológica (IRSIN-FRIAT), Hospital Central de Asturias, 33006 Oviedo, Spain. ecoto@hcas.sespa.es
authors.forename: Eliecer
authors.initials: E
authors.lastname: Coto
authors.forename: Julián R
authors.initials: JR
authors.lastname: Reguero
authors.forename: Victoria
authors.initials: V
authors.lastname: Alvarez
authors.forename: Blanca
authors.initials: B
authors.lastname: Morales
authors.forename: Alberto
authors.initials: A
authors.lastname: Batalla
authors.forename: Pelayo
authors.initials: P
authors.lastname: González
authors.forename: María
authors.initials: M
authors.lastname: Martín
authors.forename: Mónica
authors.initials: M
authors.lastname: García-Castro
authors.forename: Gustavo
authors.initials: G
authors.lastname: Iglesias-Cubero
authors.forename: Arturo
authors.initials: A
authors.lastname: Cortina
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000235:genetics*; D009419:Nerve Tissue Proteins; D011110:Polymorphism, Genetic; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000235:genetics*; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins
chemical_list: D002352:Carrier Proteins; D008055:Lipids; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin