Variation at the beta-1 adrenoceptor gene locus affects left ventricular mass in renal failure.

OBJECTIVES: To examine the relationship between this variation in the beta1AR gene and the effect on LV mass. BACKGROUND: Left ventricular (LV) mass is an important cardiovascular risk factor. Beta-1 adrenoceptors (betaAR) are predominately located in the heart and their variation may, therefore, affect LV mass. A known polymorphism of the betaAR changes the amino acid at position 389 from glycine to arginine within an area critical for G-protein coupling and so cell signalling. The arginine-form of the receptor has been demonstrated to have increased GTP binding. METHODS: We studied 249 patients attending a renal clinic, 37% of whom were on renal replacement therapy (RRT). Raw LV mass was calculated by echocardiography. LV mass index (LVMI) and LV mass indexed to height2.7 were derived thereafter. Individuals were genotyped for the beta1AR variation and categorised CC if both alleles encoded for arginine at position 389, GG if both alleles encoded for glycine and CG if heterozygous. RESULTS: There was a highly significant difference in raw LV mass, LV mass index and LV mass indexed to height2.7 between the GG group when compared to both the CC and CG genotypes groups (p<0.05). The strength of the relationship was maintained when patients on RRT or taking beta-blockers were excluded (p<0.05). CONCLUSIONS: These data suggest that genetic variation at this locus is of importance in defining left ventricular mass.

The Y chromosome effect on blood pressure in two European populations.

Higher blood pressure (BP) in males compared with females is well documented and is thought to be influenced in part by the Y chromosome. To examine whether there is an association between BP and a polymorphic HindIII biallelic marker in the nonrecombining region of the Y chromosome, we genotyped 155 males from a Polish study group and 762 males from a Scottish study group. We also tested for possible interaction between the Y chromosome and a mutation in the steroidogenic factor binding site of the aldosterone synthase gene by genotyping the same group from Scotland. There was no significant difference in age or body mass index between 2 Y chromosome genotypes in both study groups. Men with the HindIII(+) genotype had significantly higher systolic and diastolic pressures than those with the HindIII(-) genotype in both the Polish and Scottish studies. This difference between the genotypes was 5.27 mm Hg (P=0.0014) and 3.14 mm Hg (P=0.0005) for adjusted systolic BP and 2.6 mm Hg (P=0.0045) and 1.44 mm Hg (P=0.0084) for adjusted diastolic BP in the Polish and the Scottish studied, respectively. On binary logistic regression analysis, males with the HindIII(+)/TT SF1 genotype combination had an odds ratio for elevated BP of 3.92 (CI 1.21 to 12.68, P=0.023). Our results indicate that the Y chromosome harbors a locus or loci that contribute to BP variation in hypertensive and normotensive men. The polymorphism in the aldosterone synthase gene may interact with the Y chromosome to increase the odds of an individual's developing higher BP.