Serotonin Receptor 2A (HTR2A) Gene Polymorphisms Are Associated with Blood Pressure, Central Adiposity, and the Metabolic Syndrome

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Abstract
Background: Although the etiology of the metabolic syndrome remains unclear, recent evidence suggests that dysregulation of brain serotonergic activity may partly underlie the covariation of risk factors comprising the syndrome. In addition, prior studies have shown polymorphisms in the serotonin 2A receptor (HTR2A) gene to be associated with two syndrome components, hypertension and central adiposity. We conducted a study to confirm associations of HTR2A polymorphisms with elevated blood pressure and central adiposity and tested for association between these polymorphisms and the metabolic syndrome. Methods: The study sample included 934 unrelated individuals of European ancestry. We tested for association of two HTR2A polymorphisms, one in the promoter: (−1438[G/A]) and one in the first intron (2416 [C/T]), individually and as a diplotype, with elevated blood pressure, central adiposity, elevated fasting glucose, triglycerides, high density lipoprotein (HDL) cholesterol and presence of the metabolic syndrome, as defined by the American Heart Association/National Heart, Lung and Blood Institute (AHA/NHLBI) Scientific Statement Executive Summary. Results: Confirming previous reports, elevated blood pressure (>130/85 mm Hg) was associated with both the −1438 GG and 2416 TT genotypes and the GG/TT diplotype (ORs = 1.39–1.76); high waist circumference was associated with −1438 GG genotype only (OR = 1.57). In addition, both the −1438 GG and 2416 TT genotypes, and the GG/TT diplotype, predicted presence of the metabolic syndrome (ORs = 1.44–1.77). Fasting glucose, triglyceride and HDL cholesterol were not associated with either polymorphism. Conclusions: Elevated blood pressure, central adiposity, and the metabolic syndrome are associated with polymorphisms in HTR2A gene.