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.

Interaction of Serotonin Transporter Gene-Linked Polymorphic Region and Stressful Life Events Predicts Cortisol Stress Response

“…Instead, both studies have shown that homozygous long allele carriers exhibit markedly different behavioral and neural responses to social stressors, visual stimuli, and in the scanner at rest, depending on their early life stress history. This may explain why some studies associated the L allele with less favorable phenotypes, such as increased cardiovascular reactivity, greater risk of myocardial infarction (Coto et al, 2003;Fumeron et al, 2002;Williams et al, 2001), increased risk of psychosis (Goldberg et al, 2009), and increased risk of chronic PTSD (Grabe et al, 2009;Lee et al, 2005;Thakur et al, 2009). In light of these results, it is possible that, in the absence of early SLEs, homozygous L allele carriers are susceptible to multiple physical and psychological adverse outcomes.…”

Lack of Association between Endothelin-1 Gene Variants and Myocardial Infarction

“…Thus, our data are relevant for the effect of EDN1 variants on early-onset MI among male smokers, but we cannot rule out a gender-dependent effect, or an effect at older ages or linked to other risk factors. The strength of a genetic effect can vary by age, causing "age-varying associations", and an age-dependent effect for some polymorphisms on MI risk has been reported [41][42][43] . Finaly, our patients were survivors of a first MI episode, and we cannot exclude that EDN1 variants play a significant role in fatal MI, or contribute to the risk of recurrent MI episodes.…”

Association of HTTLPR and 5-HT2A T102C polymorphisms with smoking characteristics and anthropometric profiles of Thai males

“…For analysis of the T102C polymorphism of the 5-HT 2A receptor gene, forward primer -5'-TCTGCTACAAGTTCTGGCTT-3' and reverse primer -5'-CTGCAGCTTTTTCTCTAG GG-3', were used; PCR was conducted in 50 mL according to the protocol described by Coto et al (2003). Each reaction product was digested with the restriction enzyme MspI, and electrophoresed on a 3% (w/v) agarose gel.…”