**5. Conclusions**

*The Recent Topics in Genetic Polymorphisms*

mass index, and Wigle score.

**4.5** *CYP11B2* **genotypic variants and heart failure**

susceptibility, therapeutic response, or prognosis of HF.

mented in the presence of the TT genotype.

mRNA levels show sevenfold increase in the cardiac tissue of HCM patients when compared normal cardiac tissue [93]. It exerts its action via stimulation of mineralocorticoid receptor resulting in enhancement of myocardial cell hypertrophy, progressive myocardial fibrosis leading to ventricular and septal remodeling, and hypertrophy, resulting in elevated ventricular mass observed in HCM patients [94, 95]. Therefore, genetic variations involving *CYP11B2* gene might influence the structure and function of the left ventricle via increasing aldosterone secretion [93]. Several polymorphisms in the *CYP11B2* had been described in the HCM with −344C>T and intron 2 conversion have significant associations with left ventricular size, mass, and function in different population studies. However, the −344C>T promoter polymorphism is a much better predictor of left ventricular size than is the intron 2 gene conversion [96]. The −344C>T polymorphism have proved to be associated with the risk for HCM progression in many previous studies [93, 94, 97–99], whereas no association has suggested by other studies [100, 101].This controversy extents to the risk allele, which may be the −344C in some studies [96, 98–100, 102, 103] or −344T in another study [97]. Moreover, the risk allele for increased ventricular size and thickness differs regarding gender as with a study by Chai et al., [97] in which the T allele carrier is associated with a significantly higher intra-ventricular septum thickness in males, whereas in females, CC genotype carriers had a higher risk for increased intra-ventricular mass thickness, left ventricular

Heart failure (HF) is a cardiac disorder characterized by cardiac remodeling with subsequent cardiac dysfunction [104]. It is a multifactorial disease, which is precipitated due to underlying cardiac disorders as hypertension, CAD, valvular dysfunction, arrhythmia, and cardiomyopathy. Integrated neuronal and hormonal elements are involved in the pathogenesis of HF including activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system, and other mediators as endothelin, vascular endothelial growth factor, and inflammatory cytokines. Based on the previously described neurohormonal factors, therapeutic approaches for HF have developed to block these factors including angiotensinconverting enzyme inhibitors (ACEI), and aldosterone antagonists [105]. Several risk and prognostic factors have influenced the progression of chronic congestive heart failure (CHF) including age, New York Heart Association (NYHA) class, renal function, and comorbidities such as atrial fibrillation, diabetes mellitus, and ischemic heart disease [106]. However, genetic elements seem to affect the risk, severity, and therapeutic response of HF [107]. *CYP11B2* polymorphisms specifically −344C/T is among these genetic factors and has been associated with the

A study by McNamara et al. [108] was performed on a total of 354 subjects from A-HeFT (African American Heart Failure Trial). They detected a higher frequency of −344 TT genotypes carriers (61%) than CC genotypes carriers (6.2%) in African Americans. Also, the −344 C allele was associated with significantly poorer HF hospitalization-free survival and a higher rate of death. Moreover, the therapeutic influence of nitric oxide donor (isosorbide dinitrate and hydralazine) was aug-

Another study by Feola et al. [109] on 175 patients from the European continental ancestry congestive heart failure (CHF) population and revealed that no significant differences between −344 CC and −344 TT genotypes carriers regarding cardiac output, end-systolic or diastolic left ventricle diameter, left ventricular ejection fraction (LVEF), and pro-natriuretic peptide (BNP). Also, −344 C allele

**30**

*CYP11B2* gene polymorphism is associated with increased cardiovascular risk via enhancing aldosterone synthesis and production which acts either systemically or locally on the heart. There is a large number of polymorphisms has been identified for *CYP11B2*. Among them, **−**344C/T polymorphism was extensively studied in different ethnic groups and has proved to be associated either solely or synergistic with other *CYP11B2* polymorphisms in the risk for progression and susceptibility of several cardiovascular disorders as hypertension, AF, CAD, cardiomyopathy, and HF. Also, *CYP11B2* polymorphisms were confirmed as a predictor for survival and therapeutic response in some cardiovascular disorders as hypertension and HF. Moreover, gene-environment interactions of *CYP11B2* were suggested in several studies but still need to be confirmed.
