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The amino-terminal polymorphisms, Arg16Gly and Gln27Glu, of the β2-adrenergic receptor (β2AR) have been shown to affect regulation of the receptor expression by an agonist in cell culture studies. The Arg16Gly polymorphism has also been recently shown to be associated with essential hypertension. We therefore evaluated whether the amino-terminal polymorphisms of β2AR are associated with hypertension in a Caucasian population.We performed an association study in 298 hypertensive patients and an equal number of age-matched normotensive controls from the East Anglian region, with blood pressure assessed categorically and quantitatively. We also examined the influence of the amino-terminal polymorphisms on blood pressure response to β-blockade in 144 of the patients randomly assigned to this class of drug. Genotyping of the Arg16Gly polymorphism was undertaken by a newly designed mismatched polymerase chain reaction (PCR) and digestion with Nde I, whereas the Gln27Glu polymorphism was genotyped by PCR followed by Fnu4H I cleavage.We found no differences in the genotype or allele frequencies of the β2AR polymorphisms between hypertensive and normotensive participants. There was also no association between the β2AR genotypes and variations in either basal blood pressure or the blood pressure response to a β-blocker.These findings suggest that the amino-terminal polymorphisms of the β2AR gene are unlikely to constitute major susceptibility for essential hypertension in the East Anglian population.