Association study of the 5-HT2A receptor gene polymorphism, T102C and essential hypertension

Background: Serotonin dysfunction has been implicated in hypertension due t o its ability to induce vasoconstriction via stimulation of 5-HT2 receptors and due to the antihypertensive effect of ketanserin, an antagonist at the 5-HT2A receptor subtype, expressed both on arteries and the brain, The sil ent T102C polymorphism in the 5-HT2A gene is in absolute linkage disequilib rium with a polymorphism in the promoter and may contribute to genetic pred isposition possibly by modifying the transcription of the gene, Objective: To examine the genetic contribution of the T102C 5-HT2A polymorp hism in essential hypertension in a case-control sample of UK residents. Design: The hypertensive group consisted of 342 subjects over 75 years and the community-based control group consisted of 319 subjects, Subjects were genotyped for the T102C polymorphism by Mspl restriction enzyme digestion f ollowing PCR amplification. Results: Sex-specific association analysis revealed significant differences between hypertensive and normotensive subjects in the genotypes distributi on (P = 0.016) and allelic frequencies (P = 0.007) in the female group, The direction of significance was increased frequency of the 102-C allele in t he hypertensive subjects, There were no association between haplotype and a ge or body mass index, which suggest that the effect of the T102C variant i s not influenced by these variables, Conclusion: This data indicates that the T102C polymorphism in the 5-HT2A g ene might be an independent risk factor for increased blood pressure in fem ale individuals with essential hypertension.