Carotid and Femoral Artery Stiffness in Relation to Three Candidate Genes in a White Population

Abstract

Abstract-Different genetic polymorphisms influence cardiovascular disease. We recently discovered a relationship between the intima-media thickness of the muscular femoral artery, but not the elastic common carotid artery, and the combined ACE (ACE, I/D), ␣-adducin (Gly460Trp), and aldosterone synthase (AS, CϪ344T) gene polymorphisms. To investigate the relationship between these polymorphisms and functional properties of the carotid artery and femoral artery, a sample of 756 subjects enrolled in a population study were genotyped for the presence of the ACE D, ␣-adducin 460Trp, and aldosterone synthase Ϫ344T alleles. Vessel wall properties were assessed using a vessel wall movement detector system in combination with applanation tonometry. Statistical analysis allowed for confounders and interaction among genes. Cross-sectional compliance of the common carotid artery was negatively associated with the ACE D allele. ACE II versus ACE DD homozygotes differed, expressed as a percentage of the population mean (7.0%; 95% confidence interval [CI], 1.6% to 12.4%; Pϭ0.02). In multigene analysis, ACE DD subjects also deviated significantly from the population mean for the distensibility coefficient of the common carotid artery when carrying the AS/T allele (Ϫ5.5%; 95% CI, Ϫ9.3% to Ϫ1.7%; PϽ0.01), without a change in cross-sectional compliance. ACE DD subjects, when homozygote for ␣-adducin Gly460, had a lower femoral cross-sectional compliance (Ϫ10.4%; 95% CI, Ϫ1.9% to Ϫ18.9%; PϽ0.03) and a lower distensibility (Ϫ9.7%; 95% CI, Ϫ2.1% to Ϫ17.3%; PϽ0.02) compared with the population mean. These data show that functional large artery properties are influenced by the ACE I/D polymorphism. Cross-sectional compliance and distensibility coefficients are influenced by the ACE I/D genotype, but this influence depends on the vascular territory and genetic background.

Renal function in relation to three candidate genes in a Chinese population

“…In the same population the ACE I/D, a-adducin Gly460Trp and aldosterone synthase 344C/T polymorphisms showed significant interactions in relation to the intima-media thickness of the femoral artery [2] and the incidence of hypertension [3]. The hypothesis underlying our previous studies [1,2,3,4] was that these three candidate genes and their interactions lead to structural and/or functional changes in the cardiovascular-renal system via their influence on sodium reabsorption in the kidney and the circulating fluid volume.…”

Apparent Treatment-Resistant Hypertension and Chronic Kidney Disease: Another Cardiovascular-Renal Syndrome?

“…32 Furthermore, increased aortic stiffness as assessed by pulse wave velocity is independently predictive of increase morbidity, CV mortality, and all-cause mortality in patients with hypertension. 33,34 Although the exact mechanisms of aortic stiffening are incompletely understood, blood aldosterone synthase, ACE polymorphisms, [35][36][37] and volume status have been independently associated with pulse wave velocity. 38 Given the roles of aldosterone, angiotensin, and volume expansion in CKD, it is unsurprising that patients with CKD have increased aortic stiffness.…”

Arterial properties in relation to genetic variation in α-adducin and the renin–angiotensin system in a White population

“…In smokers, median tobacco use was 14 cigarettes per day (interquartile range, [8][9][10][11][12][13][14][15][16][17][18][19][20]. In drinkers, the median alcohol consumption was 10 g day À1 (interquartile range, [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Table 2 lists the arterial properties by generation and vascular territory.…”

“…5 Moreover, in ACE DD homozygotes, carriers of mutated ADD1 had higher femoral distensibility and cross-sectional compliance than those with the wild-type ADD1. 6 In the prospective Flemish Study on Environment, Genes and Health Outcomes, the combination of ACE DD homozygosity and mutated ADD1 worsened cardiovascular prognosis to a similar extent as classical risk factors. 7 Experimental studies in fibroblasts from 51 subjects and in transfected cell models showed higher membrane-bound ACE activity in cells carrying the ADD1 Trp allele.…”

“…7 Experimental studies in fibroblasts from 51 subjects and in transfected cell models showed higher membrane-bound ACE activity in cells carrying the ADD1 Trp allele. 7 In view of the aforementioned evidence, [1][2][3][4][5][6][7] we hypothesized that arterial properties might be related not only to interactions of ADD1 with ACE, but also to interactions of ADD1 with other genes encoding various components of the renin-angiotensin system. We therefore genotyped Flemish Study on Environment, Genes and Health Outcomes participants for the angiotensinogen (AGT) C-532T and G-6A promoter polymorphisms as well as for the intronic A1166C polymorphism in the angiotensin II type-1 receptor gene (AT1R).…”