Association study of the 5-HT_2A receptor gene polymorphism, T102C and essential hypertension

Abstract

Background: Serotonin dysfunction has been implicated in hypertension due to its ability to induce vasoconstriction via stimulation of 5-HT₂ receptors and due to the antihypertensive effect of ketanserin, an antagonist at the 5-HT_2A receptor subtype, expressed both on arteries and the brain. The silent T102C polymorphism in the 5-HT_2A gene is in absolute linkage disequilibrium with a polymorphism in the promoter and may contribute to genetic predisposition possibly by modifying the transcription of the gene.

Objective: To examine the genetic contribution of the T102C 5-HT_2Apolymorphism 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 following PCR amplification.

Results: Sex-specific association analysis revealed significant differences between hypertensive and normotensive subjects in the genotypes distribution (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 the hypertensive subjects. There were no association between haplotype and age or body mass index, which suggest that the effect of the T102C variant is not influenced by these variables.

Conclusion: This data indicates that the T102C polymorphism in the 5-HT_2A gene might be an independent risk factor for increased blood pressure in female individuals with essential hypertension.