Polymorphisms in candidate genes for blood pressure regulation in young men with normal or elevated screening blood pressure

We have previously shown correlations between cardiovascular risk factors s uch as blood pressure (BP), sympathetic nervous system activity, lipids and insulin resistance in young men with elevated screening BP. In the present study we aimed to: (I)compare the genotype distribution and allele frequen cies of Ii polymorphisms in seven candidate genes for BP regulation in heal thy 21-year-old Caucasian men, between 18 men with normal and 67 men with h igh screening BP, and (2) evaluate the effect of these polymorphisms in can didate genes on casual BP, BP responses to mental stress or catecholamines and metabolic parameters including insulin sensitivity. There were no diffe rences in genotype distributions or allele frequencies between the subjects with normal and those with high screening BP. Insulin sensitivity was sign ificantly higher in GG homozygotes in the G-261A polymorphism at the alpha 2A-adrenergic receptor (alpha (2A)AR) locus compared to GA heterozygotes (p = 0.007). Subjects who were homozygous both GG in the G-261A polymorphism at the alpha (2A)AR locus and GlyGly in the Arg16Gly polymorphism Lit the b eta (2)-adrenergic (beta (2)AR) receptor loci had significantly higher insu lin sensitivity and lower catecholamine levels during mental stress than su bjects with other genotypes. Subjects who were II homozygous at the angiote nsin converting enzyme (ACE) locus and AA homozygous at the angiotensin typ e I receptor (AT1R) locus had lower BP and a better lipid profile than the rest of the group. Thus, in this explorative study, we report an associatio n between insulin sensitivity and a polymorphism at the alpha (2A)AR locus. We suggest the presence of gene-gene interactions in the renin-angiotensin system and the sympathetic nervous system.