Genetic polymorphisms and heart failure (original) (raw)
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Role of ?1- and ?2-adrenoceptor polymorphisms in heart failure: a case-control study
European Heart Journal, 2004
Background We hypothesised that the polymorphisms of the genes encoding for b1and the b2-adrenoceptors may have a role in the pathogenesis of heart failure (HF). We therefore compared the polymorphisms of the b1-adrenoceptor gene (Arg389Gly), the b2-adrenoceptor gene (Arg16Gly, Gln27Glu) and their combinations in patients with HF and normal subjects living in the same area. Methods and results A total of 256 cases with HF (left ventricular ejection fraction 6 40%) and 230 normal subjects were enrolled. The b1-and b2-adrenoceptor gene polymorphisms were assessed by PCR, followed by restriction enzyme digestion. No differences were observed in the distribution of any of the three genotypes studied in patients with HF and normal subjects. An analysis of the genotype combinations showed a non-significant increase in the risk of HF associated with the Arg389-Gly16Gln27 (odds ratio = 1.4; 95%CI 0.5-3.6) and Arg389Gly16 Glu27 (odds ratio = 1.2; 95%CI, 0.5-2.8) homozygous allele combinations. Conclusion None of the three most common polymorphisms of b-adrenoreceptors are associated with an increased risk of HF.
RAAS and adrenergic genes in heart failure: Function, predisposition and survival implications
World journal of cardiology, 2010
It is well appreciated that several neurohormones and signaling cascades are activated that promote long-term deterioration of cardiac function and structure. Activation of the renin-angiotensin-aldosterone system (RAAS) and the adrenergic system is closely related to heart failure. Common gene variants that encode neurohormonal, adrenergic and intracellular proteins have been demonstrated to modulate the course and consequences of heart failure. However, the literature is replete with conflicting results and it remains uncertain as to whether particular gene variants predispose heart failure. Therefore, the main purpose of this review was to discuss the effects of single nucleotide polymorphisms (SNPs) that are located in genes encoding elements of the RAAS and the adrenergic system on the predisposition to and survival from heart failure. Most studies indicate that common SNPs encoding elements of the RAAS and the adrenergic system do not predispose individuals to heart failure. C...
Clinical and Experimental Hypertension, 2017
Background: Heart failure with preserved ejection fraction (HFpEF) has close ties with hypertension, though risk factors to the development of HFpEF in hypertensive patients are not fully understood. Left ventricular hypertrophy (LVH) signifies the susceptibility toward diastolic heart dysfunction, and genetic determinants of LVH as a result may serve as risk predictors for HFpEF in hypertension. We investigated the role of three renin-angiotensin-aldosterone system (RAAS) gene polymorphisms in the development of LVH in hypertensive patients with a diagnosis of HFpEF. Methods: A total of 176 hypertensive patients with a diagnosis of HFpEF were divided to cases with LVH and controls without. rs4343 and rs4291 of angiotensin-converting enzyme (ACE) and rs5186 of angiotensin receptor type 1 were genotyped using PCR-RFLP method. Results: Genotypes and allele frequencies were significantly different between the case and control groups for rs4343 and rs4291, whereas no difference was observed for rs5186.Conclusion: Increased ACE activity explains the significant association of rs4343 and rs4291 polymorphisms with LVH in the carriers. Furthermore, findings support the pathophysiologic links between RAAS and increased LV mass in hypertension and suggest a genetic susceptibility to HFpEF. Such polymorphisms may serve as risk predictors of HFpEF in hypertensive patients.
Renin-Angiotensin Aldosteron System Genes Polymorphisms and Acute Heart Failure
Biomedical Journal of Scientific & Technical Research, 2021
The Renin Angiotensin Aldosteron System (RAAS) is one of the major systems involved in the pathophysiology of heart failure. In this study we investigate the association between the renin angiotensin aldosteron system genes polymorphisms and acute heart failure (AHF) and we evaluate the role of serum ACE activity. Methods: We included 300 patients over 20 years old admitted to the Emergency Department for acute dyspnea. According to the clinical findings and results of the B-type natriuretic peptide (BNP level), patients were divided into two groups: heart failure (HF) and non-heart failure (non-HF) groups. Genotyping was done by PCR-RFLP. The level of serum ACE activity was determined by spectrophotometric method using hippuryl histidyl leucine. We found the diagnosis of AHF in 50% of the population. Results: No association between the renin polymorphism and AHF, but we found an association between ACE ID and CYP11B2 polymorphisms and heart failure. Level of serum ACE activity is significantly higher in the group of AHF. Conclusion: We can conclude that blood ACE activity, ACE ID and CYP11B2 can be a marker of acute heart failure.
2010
In the present study, we aimed to evaluate the effect of adrenergic receptor polymorphisms on the response of myocardium to measured levels of cardiac adrenergic drive, and to evaluate whether polymorphisms of presynaptic adrenoceptors modified the rate of cardiac and systemic release of norepinephrine. BACKGROUND Heightened sympathetic activity plays an important pathophysiologic role in congestive heart failure (CHF). Recently several functionally relevant polymorphisms of the ␣ 2-,  1-, and  2-adrenoceptors have been identified, and specific genotypes have been associated with the incidence or clinical severity of CHF. These adrenoceptors are known to be located both pre-synaptically (␣ 2 and  2) and post-synaptically ( 1 and  2), raising the possibility that their association with clinical measures in CHF could be mediated either by modulation of the cardiac response to a given level of adrenergic drive or by altering norepinephrine release from sympathetic nerve terminals. METHODS We determined the  1-,  2-, and ␣ 2C-adrenoceptor genotype in 60 patients with severe CHF in conjunction with measurement of cardiac and systemic sympathetic activity using the radiotracer norepinephrine spillover method. RESULTS We showed a strong relationship (r ϭ 0.67, p Ͻ 0.001) between heart rate and the level of cardiac adrenergic drive, and heart rate for a given level of cardiac adrenergic drive was substantially greater in patients with the Arg/Arg16  2-adrenoceptor polymorphism (p ϭ 0.02), whereas no such relationship existed for polymorphisms of the  1-adrenoceptor. The genotype of the ␣ 2C-and  2-adrenoceptors showed no relationship to the rate of norepinephrine release from cardiac sympathetic nerves. CONCLUSIONS For the first time, we show that  2-adrenoceptor polymorphisms significantly influence the relationship between heart rate and cardiac adrenergic drive in CHF, but do not affect the rate of norepinephrine release from sympathetic nerve terminals.
European Journal of Heart Failure, 2006
Background: Adrenergic activation has a central role in the development of HF. The function of the h 1 -and the a 2C -adrenergic receptors is influenced by gene polymorphisms: the h 1 Arg389 variant is associated with increased h 1 -receptor sensitivity and the a 2C -receptor Del322-325 variant is associated with decreased a 2C receptor function and increased norepinephrine release. We hypothesised that these polymorphisms could influence the prevalence of heart failure. Methods: The role of the h 1 -and a 2C -adrenergic receptor gene polymorphisms as risk factors for heart failure (HF) was assessed in an Italian white Caucasian population using a case-control study design. Genomic DNA was analysed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RLFP). Results: We compared 260 Caucasian patients with HF and 230 normal subjects. The h 1 Arg389 allele was frequent both in the patients with HF (69%) and in the normal subjects (73%). The a 2C Del322-325 variant was rare in both groups (9% and 8%, respectively). Patients homozygotes for either the h 1 Arg389 or the a 2C Del322-325 alleles had no increased risk of HF (odds ratio [OR], 0.8; 95%CI: 0.5 -1.2 and OR, 0.8; 95% CI: 0.4 -1.8, respectively). Patients homozygotes for both the h 1 Arg389 and the a 2C Del322-325 alleles had no increased risk of HF as well (OR: 0.6; 95% CI: 0.2 -2.1). Conclusions: h 1 -ARs and a 2C -ARs polymorphisms are not associated with an increased risk of HF in an Italian white Caucasian population.
Cardiology, 2010
Studies on the association between genetic polymorphisms and personality disorders have provided inconsistent results. Using the "enriched sample method," the authors of the present study aimed to assess the association between polymorphisms in the serotonergic transmitter system and comorbid personality disorders in patients recently diagnosed with first-episode depression. A total of 290 participants were systematically recruited via the Danish Psychiatric Central Research Register. Diagnoses of personality disorders were assessed by a SCID-II interview, and polymorphisms in the genes encoding the serotonin transporter, serotonin receptors 1A, 2A, 2C, and tryptophan hydroxylase 1 were genotyped. The authors found a significant effect of the length polymorphism in the serotonin transporter gene (5-HTTLPR) on cluster B personality disorder (mainly borderline disorder), but no influence on cluster C personality disorder, and no associations between other polymorphisms and personality disorders. The study adds evidence to the effect of the serotonin transporter gene specifically on cluster B personality disorders.