Objective: The aim of this study was to investigate the relationships between F216L (rs28942112), R496W (rs374603772), S127R (rs28942111), and D374Y (rs137852912) PCSK9 gain-of-function (GOF) mutations and primary dyslipidemia and serum lipid levels in patients with primary dyslipidemia.
Methods: In this case-control study, DNA was isolated from blood samples collected from patients diagnosed with primary dyslipidemia in cardiology outpatient clinic of Ege University (n=200) and healthy individuals (n=201). F216L, R496W, S127R, and D374Y GOF mutations in the PCSK9 gene were evaluated and genotyped according to the results of melting curve analysis performed in a real-time polymerase chain reaction (PCR) 480 instrument using specific primers for each mutation.
Results: There were statistically significant differences between the patient and individuals in control groups in the R496W and D374Y mutations (χ2=10.742 p=0.005; χ2=6.078 p=0.048, respectively). In addition, triglyceride levels in patients with primary dyslipidemia heterozygous for R496W and D374Y mutations were 12.8-fold (p=0.015) and 3.4-fold (p=0.03) higher than that in mutant and wild-type genotype, respectively. Additionally, in the entire study group (n=401), PCSK9 R496W and D374Y mutation carriers had increased total cholesterol (p=0.021), triglycerides (p=0.0001), HDL cholesterol (p=0.028), and low-density lipoproteins (LDL) cholesterol (p=0.028) levels. However, F216L (rs28942112) and S127R (rs28942111) mutations were not detected in patients with primary dyslipidemia and healthy controls.
Conclusion: We conclude that the PCSK9 R496W (rs374603772) and D374Y (rs137852912) GOF mutations may be significant risk factors in the development of primary dyslipidemia and may have significant impact on lipid parameters in general population.