Key result
The HTR2A T102 homozygosity was associated with 38% higher mean platelet aggregation compared to carriers of the 102 C-allele (39.5 vs 28.7 mm; p<0.05).
Why the study?
Does the HTR2A T102C polymorphism alter serotonin-mediated platelet function ex vivo in healthy volunteers?
Observational (n=37)
No
Does the HTR2A T102C polymorphism alter serotonin-mediated platelet function ex vivo in healthy volunteers?
Absolute Event Rate: 39.5% vs 28.7%
p-value: p=<0.05
The T102 homozygosity in the HTR2A gene is associated with increased serotonin-mediated platelet aggregation, offering a mechanistic explanation for its previously reported association with acute myocardial infarction.
May underlie prior MI associations; hypothesis-generating for HTR2A genotyping in thrombotic risk but should not change practice.
Although the environmental and life-style factors influencing individual predisposition to acute myocardial infarction (AMI) have been well documented, little is known on the identity of genetic loci that may contribute to risk for AMI. Recently, genetic studies in patients with nonfatal AMI have suggested an association with the T 102 C polymorphism in the serotonin 5-HT(2A) receptor gene (HTR 2 A). Considering the significant role of the 5-HT(2A) receptor in serotonin-induced platelet responses and the contribution of platelet (patho)physiology to thromboembolic events, we postulated that the increased susceptibility to AMI in patients with the T 102 homozygosity may be attributable, in part, to altered serotonin-mediated platelet function. In a group of healthy volunteers recruited from the Eskisehir region in central Turkey (N=37), we investigated the functional consequences of HTR 2 A T 102 C polymorphism in relation to platelet pharmacodynamics ex vivo. The platelet shape change and aggregation response to serotonin were measured with use of the platelet aggregometry and expressed as aggregometer output (mm). Because the circulating catecholamine hormone epinephrine can augment platelet aggregation, pharmacodynamic response (aggregation and its inhibition by 5-HT(2A) receptor antagonist cyproheptadine) was measured in the presence of both serotonin and epinephrine, to mimic the clinical situation in patients. The mean platelet aggregation was higher by 38% in subjects with T 10 2 homozygosity (T/T genotype, N=13) when compared with the carriers of the 102 C-allele (T/C and the C/C genotypic groups, N=24) (39.5 mm+/-12.3 vs. 28.7 mm+/-16.8, respectively) (mean+/-SD) (p<0.05). On the other hand, neither the serotonin-induced platelet shape change nor the cyproheptadine inhibition of platelet aggregation was influenced by the HTR 2 A T 102 C genetic variation (p>0.05). These findings in healthy subjects may provide a mechanistic explanation for the previously reported genetic association between HTR 2 A and AMI. Further genetic association studies of the 5-HT(2A) receptor in patients with AMI in different populations are warranted.
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Erol et al. (2005) conducted an observational in Healthy volunteers (n=37). HTR2A T102 homozygosity (T/T genotype) vs. Carriers of the 102 C-allele (T/C and C/C genotypes) was evaluated on Mean platelet aggregation in response to serotonin and epinephrine (mm) (p=<0.05). The HTR2A T102 homozygosity was associated with 38% higher mean platelet aggregation compared to carriers of the 102 C-allele (39.5 vs 28.7 mm; p<0.05).
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