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Journals / The Anatolian Journal of Cardiology / 2017 / Cilt: 18 - Sayı: 4

PCSK 9 gain-of-function mutations (R496W and D374Y) and clinical cardiovascular characteristics in a cohort of Turkish patients with familial hypercholesterolemia

Esra KAYA
LATİFE MERAL KAYIKÇIOĞLU
ASLI TETİK VARDARLI
FATMA ZUHAL EROĞLU
Serdar PAYZIN
LEVENT HÜRKAN CAN
Pages
266–272
DOI
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AI Summary & Key Takeaways

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⚡ TL;DR(Too Long; Didn't Read)

There was no significant difference with regard to demographic characteristics and CV disease risk factors and clinical course of the disease between the PCSK9 mutation-positive and PCSK9 mutation-negative groups.Conclusion: This is the first study from a Turkish FH cohort, revealing a higher frequency (approximately 14%) of two PCSK9 GOF mutations (D374Y and R496W) and a different disease course compared to the world literature.

📌 3 Key Takeaways

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Objective & Hypothesis:Objective: The molecular basis of the mutations in the PCSK9 gene that produces familial hypercholesterolemia (FH) in the Turkish population is unknown.
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Key Findings & Data:This study was conducted to determine the presence of four different PCSK9 gain-of-function (GOF) mutations (F216L, R496W, S127R, and D374Y) in a group of patients with FH.Methods: A total of 80 consecutive patients with FH (mean age: 56±11 years; mean maximum LDL cholesterol: 251±76 mg/dL) were included in the study.
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Conclusion & Impact:There was no significant difference with regard to demographic characteristics and CV disease risk factors and clinical course of the disease between the PCSK9 mutation-positive and PCSK9 mutation-negative groups.Conclusion: This is the first study from a Turkish FH cohort, revealing a higher frequency (approximately 14%) of two PCSK9 GOF mutations (D374Y and R496W) and a different disease course compared to the world literature.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Domain Parameters

Abstract

Objective: The molecular basis of the mutations in the PCSK9 gene that produces familial hypercholesterolemia (FH) in the Turkish population is unknown. This study was conducted to determine the presence of four different PCSK9 gain-of-function (GOF) mutations (F216L, R496W, S127R, and D374Y) in a group of patients with FH.Methods: A total of 80 consecutive patients with FH (mean age: 56±11 years; mean maximum LDL cholesterol: 251±76 mg/dL) were included in the study. Patients with FH were diagnosed according to the Dutch Lipid Clinic Network criteria based on serum cholesterol levels, personal and family histories of cardiovascular disease, tendon xanthomas, and genetic analysis. To identify F216L, R496W, S127R, and D374Y mutations of the PCSK9 gene, high-resolution melting analysis was performed on isolated DNAs.Results: : Of the 80 patients, there were 11 patients (13.8%) with PCSK9 GOF mutations. Detected mutations were D374Y mutation in four (5.0%) patients and R496W in seven patients (8.7%). Only one patient was homozygous for R496W mutation. The other two GOF mutations (S127R and F216 variants) were not detected. There was no significant difference with regard to demographic characteristics and CV disease risk factors and clinical course of the disease between the PCSK9 mutation-positive and PCSK9 mutation-negative groups.Conclusion: This is the first study from a Turkish FH cohort, revealing a higher frequency (approximately 14%) of two PCSK9 GOF mutations (D374Y and R496W) and a different disease course compared to the world literature.

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Cite This Article

KAYA, E., KAYIKÇIOĞLU, L. M., VARDARLI, A. T., EROĞLU, F. Z., PAYZIN, S., CAN, L. H. (2017). PCSK 9 gain-of-function mutations (R496W and D374Y) and clinical cardiovascular characteristics in a cohort of Turkish patients with familial hypercholesterolemia. The Anatolian Journal of Cardiology, Cilt: 18 - Sayı: 4, 266–272. https://ajindex.com/articles/365372

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