PCSK9 polymorphism rs505151 is associated with the risk of NAFLD in Iranian participants: A case-control study

Background: Gain-of-function mutations in the PCSK9 gene lead to elevated serum lipid profile levels, including low-density lipoprotein (LDL), which increases the risk of cardiovascular diseases. This study aims to investigate the relationship between selected PCSK9 gene polymorphisms and serum levels of PCSK9 enzyme in patients with non-alcoholic fatty liver disease (NAFLD) in Kurdistan province, Iran.Methods: 110 NAFLD patients and 50 healthy controls underwent biochemical assays to determine lipid profile levels, while genotyping for PCSK9 gene polymorphisms was done via RFLP-PCR and Sanger sequencing. Serum levels of PCSK9 were measured using an ELISA kit.Results: Serum PCSK9 levels were not significantly different between NAFLD patients and healthy controls. The rs778796405 and rs28362201 polymorphisms had no mutant nucleotides. The rs505151 polymorphism had a frequency of 17.2 % in NAFLD patients and 10 % in controls, with no significant difference (P > 0.05). The G allele of rs505151 was associated with higher levels of LDL, ALT, cholesterol, and BMI, and the AG genotype was associated with the severity of liver steatosis in female patients. However, the AG genotype had no significant effect on NAFLD incidence.Conclusions: The G allele of the rs505151 polymorphism in the PCSK9 gene may represent a genetic risk factor for developing fatty liver disease, with potential implications for the pathogenesis of lipid-related disorders.