**4.3** *CYP11B2* **genotypic variants and coronary artery disease**

Coronary artery disease (CAD) is a complex disorder comprised two major subsequent events: coronary atherosclerosis and myocardial infarction (MI). Despite the major progress in diagnosis of CAD, the pathogenesis and possible risk factors need further evaluation. The classical risk factors including positive family history, smoking, high body mass index, and disorders as hyperlipidemia, hypertension, and diabetes mellitus have been reported to be responsible for no more than 50% of total risk factors for CAD. Accordingly, genetic background seems also to participate in the predisposition for CAD [81].

Among the different polymorphisms described for *CYP11B2* gene, several studies have shown that the *CYP11B2* gene ˗344T>C polymorphism is associated with CAD in different ethnic groups with controversial results. Previous study on 201 CAD patients and 201 controls form Italian population have detected that *CYP11B2* polymorphism and CC genotype were associated with CAD risk in crude analysis with borderline significance which is lost by stratification to the confounding factors as smoking and family history [82]. A meta-analysis suggested that the −344T>C polymorphism in the *CYP11B2* gene might be associated with susceptibility to CAD in Caucasians and Asians [83]. A study on 609 Taiwanese male and female subjects who were unrelated and received coronary catheterization found that the C/C allele occurred more frequently in females who had CAD, and that it was associated with higher left ventricular mass (LVM) and left ventricular end diastolic diameter (LVEDD) [84]. Sharma et al. [85] also reported the association of the *CYP11B2* −344C>T polymorphism with the size of atherosclerotic plaque in the carotid artery. Neal et al. [86] suggested that −344C/T polymorphism is a cardiovascular risk factor due to its association with LV hypertrophy and decreased baroreflex sensitivity which predict the morbidity and mortality rates of MI. Others failed to find any significant association of *CYP11B2* with CAD in different populations as in an Indian population and other populations [87–89].

The underlying mechanism by which the *CYP11B2* ˗344T>C polymorphism can increase the risk for CAD remains unclear. However, it is related to its effect on increasing expression of *CYP11B2*, thereby increasing aldosterone secretion [83]. Also, the influence of gene-environment interaction has been involved as an etiological factor for CAD risk. Growing evidence has suggested the interaction between ˗344T>C polymorphism and positive smoking for enhanced CAD risk [90]. Also, Hautanen et al. [91] detected that smoking and dyslipidemia are associated risk factors for non-fatal MI in males who were carriers for *CYP11B2* −344C/T allele.
