Investigating the frequency of pcsk 9 gene polymorphism (F216l, R496W, S127R, D374Y) and its effects over coronary heart disease and clinical parameters in familial hypecholesterolemia patients

Prevalence of PCSK-9 gene polymorphisms in a cohort of Turkish patients with Familial Hypercholesterolemia Introduction: Familial hypercholesterolemia (FH) is a genetic disorder characterised with elevated serum LDL-cholesterol levels, tendon xanthomas, and premature coronary heart disease (CHD). Gain of function mutations in the PCSK 9 gene are known to cause FH. We aimed to find the prevalence of PCSK 9 mutations in a cohort of FH patients who were under long term follow-up in a lipid Clinic. Methods and Results: We studied 80 consecutive Turkish patients with FH (mean age 56±11 years, % 61 women) living in the west cost of Turkey. All patients were diagnosed according to Simon Broome Register criteria and Dutch Lipid Clinic Network Criteria. "Definite" or "possible" FH patients were included. Blood samples were collected for the analysis of PCSK 9 single nucleotid polimorfism (SNP) including S127R, D374Y, F216L and R496W variants. Among 80 patients, 11 (13,75%) patients were carrying one of these variants. R496W mutation was detected in 7 (8,75 %) and D374Y mutation in 4 (5 %) patients. Of these only 1 (1,25 %) was homozygous for the R496W mutation. Comparison of the PCSK-9 mutation positive and negative patients are shown in Table-1. Although, total-cholesterol, LDL-cholesterol, apolipoprotein-B, and lipoprotein-a levels, carotid intima media and Achilles tendon thicknesses were higher in the mutation (+) patients, the difference didn't reach statistically significant level. Conclusion: The frequency of gain of function PCSK-9 mutations (D374Y and R496W) is 13.75% in a cohort of Turkish FH patients. To the best of our knowledge, this is the first study defining the prevalence of PCSK-9 mutations in a Turkish FH cohort.