Investigation of PCSK9 Gene Polymorphisms in Two Iranian Ethnic Groups with Coronary Artery Disease in Fars Province

Background: Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9), a serine protease, plays an important role in the regulation of cholesterol metabolism. PCSK9 interacts with Low Density Lipoprotein Receptor (LDLR) on the surface of hepatocytes, promoting its lysosomal degradation, thus leading to the accumulation of cholesterol outside the cells followed by hypercholesterolemia. Objective: This study aimed to assess three polymorphisms (rs662145, rs505151, and rs562556) of the PCSK9 gene in two Iranian ethnic groups (Turk and Lur) with Coronary Artery Disease (CAD) in Fars province. Methods: In this cross-sectional study, 114 Turk and 73 Lur patients with CAD were selected based on the clinical examination by a cardiologist. The three polymorphisms were assessed by Real-Time Polymerase Chain Reaction (PCR) method using specific primers and probes. Chi-square test was used to compare the two groups regarding the qualitative variables. All analyses were performed using the SPSS 18 software and P < 0.05 was considered to be statistically significant. Results: The results revealed no significant difference between the Turk and Lur groups regarding the three polymorphisms (P > 0.05). In addition, no significant relationship was observed between the rs662145 polymorphism and clinical characteristics like family history of CAD, diabetes, Myocardial Infarction (MI), Body Mass Index (BMI), and High Density Lipoprotein (HDL) level (P > 0.05). However, a significant relationship was found between the rs505151 polymorphism and MI (P = 0.03) and Low Density Lipoprotein (LDL) level (P = 0.04) in Turk patients. Nonetheless, no significant correlation was detected between the rs505151 polymorphism and clinical parameters (P > 0.05). The results also showed no significant relationship between the rs505151 polymorphism and clinical parameters in Lur patients (P > 0.05). Analysis of the rs562556 polymorphism also revealed no significant relationship between this polymorphism and clinical characteristics in both Turk and Lur samples (P > 0.05). Conclusion: rs662145 polymorphism was associated with LDL and Triglyceride (TG) levels in both Turk and Lur samples. Besides, rs505151 polymorphism was correlated to LDL level and MI in Turk patients. Therefore, in addition to other predisposing genes to CAD, analysis of PCSK9 mutations can be used for predicting hypercholesterolemia and premature CAD.