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Apelin and leptin are factors which have a potential physiological and pathological role in cardiovascular homoeostasis. Apelin receptor (APLNR), leptin receptor (LEPR) and leptin variants may affect the vascular tone in heart or peripheral circulation, thereby predisposing patients to hypertension and coronary artery disease (CAD). The aim of the present study was to evaluate four single nucleotide polymorphisms (SNPs) of APLNR genes (rs11544374 and rs948847), LEPR (rs1137101) and leptin (rs7799039) gene in patients with CAD and hypertension.This case-control study was carried out on 286 CAD-suspected patients. The participants were divided into four subgroups including: CAD patients with no hypertension (H−CAD+), hypertensive patients with no CAD (H+CAD−), CAD patients with hypertension (H+CAD+) and non-hypertensive non-CAD subjects as control group (H−CAD−). Genomic DNA from whole blood was extracted and four SNPs were assessed using PCR-RFLP.A significant difference was found in the genotype frequency of APLNR rs11544374 gene in H+CAD+ and H−CAD+ groups compared to control subjects (P<0.001 for both comparisons). Regarding the rs1137101, the prevalence of A allele compared to G allele was significantly different among the four groups (P=0.02). Results of multinomial regression analysis indicated that G allele carriers in the recessive genetic model (AA vs. AG+GG) of rs11544374 had a significantly protective effect compared to H−CAD+ and H+CAD+after adjustment (OR=0.12; 95% CI=0.02–0.61; P=0.01 and OR=0.40; 95% CI=0.17–0.98; P=0.04, respectively).The findings of present study revealed that the APLNR rs11544374 gene polymorphism might serve as predisposing factor in CAD.