P.1.156 An analysis of the treatment patterns of bipolar disorder in the UK using a general practitioner database

Abstract

Serotonin (5-HT) induces platelet aggregation by activating its 5-HT2A receptor. Platelet uptake is mediated by the 5-HT transporter (5-HTT). A common 5-HTT promoter (5-HTTLPR) splice variant results in long (L) and short (S) alleles. 5-HTTLPR genotype has been associated with increased platelet activation and risk of MI. Variation within HTR2A gene (C1354T) that encodes the 5-HT2A receptor has also been associated with enhanced platelet aggregation. We hypothesised that 5-HTT and/or HTR2A variation may influence platelet response to aspirin in patients with stable CAD.Patients (n = 144) with stable cardiovascular disease taking aspirin were genotyped for the 5-HTTLPR and HTR2A variants. Platelet inhibition was assessed by serum thromboxane and arachidonic acid-induced platelet aggregation assay.5-HTT genotype (LL vs *S) was a significant determinant of serum TX level (8.9 ± 2.6 ng/ml vs 6.0 ± 1.6 ng/ml respectively; p < 0.02) and 5-HTT LL genotype predicted an incomplete aspirin response (serum TXB2 > 2.2 ng/ml) (p = 0.04; OR = 2.22, CI = 1.03–4.79). Odds ratio of the effect of LL genotype on TX elevation was 3.8 (95% CI 1.2–11.6) in younger patients (under 64) compared to 1.0 (95% CI = 0.3–3.8) in older subjects. LL genotype did not influence AA aggregation (p = 0.83, OR = 1.2, CI = 0.3–4.1). The HTR2A variant had no effect on TX generation (p = 0.70; OR = 1.22, CI = 0.45–3.26) nor AA aggregation (p = 0.99; OR = 1.0, CI = 0.2–4.9).In younger patients with stable CAD 5HTT LL genotype carried by almost one third of our cohort is associated with a diminished response to aspirin that may increase cardiovascular risk. Genotypic variation in platelet activation may be a contributing mechanism.