It has been proven that genetic polymorphisms

It has been proven that genetic polymorphisms can play an important role in development of hypertension and CVDs. In a Turkish population-based study, it was found that the APLNR gene (rs948847-A445C) polymorphism was not associated with coronary artery disease (CAD), but it was shown to be related to weight and blood pressure [12]. It is reported that G212A allele (rs11544374) of the APLNR is effective in preventing hypertension [13]. In another study on idiopathic dilated cardiomyopathy patients, it was found that individuals with the 212A variant of the apelin gene were significantly less likely to develop heart disease than those with homozygous 212G variants [14]. Leptin is a hormone made by adipocyte which regulates energy balance by controlling hunger. Despite the well-known function of leptin on appetite [15], its effect on reduction of blood pressure was shown [16] and the defect in the receptor signaling in mice has improved the response of regulatory T Eltrombopag Olamine sale and protection against atherosclerosis [17]. Elevated leptin level positively correlates with CVD, infusion of leptin increases arterial pressure in rats and leptin-deficient mice could not develop atherosclerosis [18]. It has been reported that serum leptin levels are associated with central arterial stiffness in CAD [19]. A broad range of various studies has given way to results about the association between leptin gene polymorphisms and obesity, as well as apelin gene polymorphisms and hypertension and CVDs. For example, Gupta et al. demonstrated the role of rs3761581 polymorphism in acute coronary syndrome [20]. The APLNR, leptin and LEPR SNPs are believed to be candidate genes for CAD as well as hypertension because of their roles in regulation of lipid metabolism, regulating the blood pressure and angiogenesis [21]. Moreover, there is little and inconsistent data regarding the impact of the APLNR, LEPR and leptin polymorphisms with the risks of CAD and/or hypertension in the sample of Iranian population. Therefore, the aim of the present study was to evaluate four SNPs within the genes encoding the APLNR (rs11544374 and rs948847), LEPR (rs1137101) and leptin (rs7799039) in patients with CAD and hypertension in a south eastern Iranian population.
Material and methods
Results
Discussion Ample body of evidence has demonstrated the molecular basis of CVDs such as hypertension, CAD, atherosclerosis, metabolic syndrome, stroke, etc., accordingly, suggesting that genetic factors play a crucial role in the pathophysiology and progression of CVDs [[23], [24], [25]]. To the best of the author's knowledge, there is no report regarding the impact of leptin, LEPR and APLNR variants on CAD and hypertension risk in the Iranian population. Therefore, we investigated the association of the four promising polymorphisms of leptin (rs7799039), LEPR (rs1137101) and APLNR (rs948847 and rs11544374) genes with CAD and hypertension. It is noteworthy that the present findings did not lend any support to the association between LEPR rs1137101, APLNR rs948847 and leptin rs7799039 polymorphisms with CAD and/or hypertension risk. However, it was indicated that APLNR rs11544374 gene polymorphism was negatively related to CAD risk. A relationship has been reported to exist between genetic defect of apelin and an increased risk of CAD in patients with hypertension [26, 27]. Additionally, apelin is said to be able to cause vasodilatation in patients with chronic heart failure [28], an effect which is endothelium-dependent [29]. In addition, genetic variation in APJ is associated with hypertension as well as BMI and the onset age of hypertension [30]. The APJ mRNA were mainly detected in the endothelium of blood vessels [31], hence the assumption that apelin may be stimulated to produce NO via endothelial nitric oxide synthase (eNOS) activation in the endothelial cells [10]. The study carried out by Falcone et al. on two rs11544374 and rs948847 polymorphisms of the APLNR gene did not produce any specific evidence which could indicate the association between both polymorphisms and CAD risk [13]. The study also revealed that there was, in patients with hypertension, a more significant increase in the frequency of the G allele than in patients with normal blood pressure. Nonetheless, in the case of rs11544374 polymorphism, it was observed that G allele frequency was significantly higher in CAD patients than control group. Contrary to the present results, the findings yielded by Falcone et al. disclosed a significant increase in the AA genotype frequency in CAD patients compared to hypertensive ones. Moreover, they drew on the assumption that rs11544374 polymorphism was not a CAD marker even though it may produce a predisposing factor for hypertension. Furthermore, Sarzani et al. showed that patients carrying A allele for rs11544374 G212A polymorphism, enjoyed a significantly lower risk of heart failure than those who were homozygous (GG) for the rs11544374 allele [14]. Yokoyama et al. and Akcılar et al. found that patients with CAD exhibited a significantly decreased plasma apelin level [32, 33]. However, regarding the APLNR rs9943582 locus, having conducted a study on the Japanese and Korean populations, Hinohara et al. did not observe a positive association between APLNR rs9943582 and CAD [34]. Although a significant association was found between APLNR rs11544374 polyorphism and CAD, this was not the case with regard to the association between APLNR genes rs11544374-G212A and rs948847-A445C, and hypertension. The discrepancy which exists between the current results and those of the previous studies was most likely due to the racial-ethnic differences.