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Journals / The Anatolian Journal of Cardiology / 2018 / Cilt: 19 - Sayı: 5

Case-control study on PCSK9 R496W (rs374603772) and D374Y (rs137852912) mutations in Turkish patients with primary dyslipidemia

FATMA ZUHAL EROĞLU
ASLI TETİK VARDARLI
ZEKERİYA DÜZGÜN
CUMHUR GÜNDÜZ
VİLDAN BOZOK ÇETİNTAŞ
LATİFE MERAL KAYIKÇIOĞLU
Pages
334–340
DOI
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⚡ TL;DR(Too Long; Didn't Read)

F216L, R496W, S127R, and D374Y GOF mutations in the PCSK9gene 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).

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Objective & Hypothesis:Objective: The aim of this study was to investigate the relationships between F216L (rs28942112), R496W (rs374603772), S127R (rs28942111), andD374Y (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 cardiologyoutpatient clinic of Ege University (n=200) and healthy individuals (n=201).
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Key Findings & Data:F216L, R496W, S127R, and D374Y GOF mutations in the PCSK9gene 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).
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Conclusion & Impact: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 developmentof primary dyslipidemia and may have significant impact on lipid parameters in general population. (
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Domain Parameters

Özet

Objective: The aim of this study was to investigate the relationships between F216L (rs28942112), R496W (rs374603772), S127R (rs28942111), andD374Y (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 cardiologyoutpatient clinic of Ege University (n=200) and healthy individuals (n=201). F216L, R496W, S127R, and D374Y GOF mutations in the PCSK9gene 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 R496Wand 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 developmentof primary dyslipidemia and may have significant impact on lipid parameters in general population. (

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Cite This Article

EROĞLU, F. Z., VARDARLI, A. T., DÜZGÜN, Z., GÜNDÜZ, C., ÇETİNTAŞ, V. B., KAYIKÇIOĞLU, L. M. (2018). Case-control study on PCSK9 R496W (rs374603772) and D374Y (rs137852912) mutations in Turkish patients with primary dyslipidemia. The Anatolian Journal of Cardiology, Cilt: 19 - Sayı: 5, 334–340. https://ajindex.com/articles/365325

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References (12)

  1. Stein EA, Giugliano RP, Koren MJ, Raal FJ, Roth EM, Weiss R, et al. Efficacy and safety of evolocumab (AMG 145), a fully human monoclonal antibody to PCSK9, in hyperlipidaemic patients on various background lipid therapies: pooled analysis of 1359 patients in four phase 2 trials. Eur Heart J 2014
  2. [CrossRef] Naoumova RP, Tosi I, Patel D, Neuwirth C, Horswell SD, Marais AD, et al. Severe Hypercholesterolemia in Four British Families With the D374Y Mutation in the PCSK9 Gene: Long-Term Follow-Up and Treatment Response. Arterioscler Thromb Vasc Biol 2005
  3. [CrossRef] Kwakernaak AJ, Lambert G, Dullaart RP. Plasma proprotein convertase subtilisin–kexin type 9 is predominantly related to intermediate density lipoproteins. Clin Biochem 2014
  4. [CrossRef] Nassoury N, Blasiole DA, Tebon Oler A, Benjannet S, Hamelin J, Poupon V, et al. The cellular trafficking of the secretory proprotein convertase PCSK9 and its dependence on the LDLR. Traffic 2007
  5. [CrossRef] Maxwell KN, Breslow JL. Adenoviral-mediated expression of Pcsk9 in mice results in a low-density lipoprotein receptor knockout phenotype. Proc Natl Acad Sci U S A 2004
  6. [CrossRef] Homer VM, Marais AD, Charlton F, Laurie AD, Hurndell N, Scott R, et al. Identification and characterization of two non-secreted PCSK9 mutants associated with familial hypercholesterolemia in cohorts from New Zealand and South Africa. Atherosclerosis 2008
  7. [CrossRef] Pisciotta L, Oliva CP, Cefalù AB, Noto D, Bellocchio A, Fresa R, et al. Additive effect of mutations in LDLR and PCSK9 genes on the phenotype of familial hypercholesterolemia. Atherosclerosis 2006
  8. [CrossRef] Cameron J, Holla ØL, Ranheim T, Kulseth MA, Berge KE, Leren TP. Effect of mutations in the PCSK9 gene on the cell surface LDL receptors. Hum Mol Genet 2006
  9. [CrossRef] Humphries SE, Whittall RA, Hubbart CS, Maplebeck S, Cooper JA, Soutar AK, et al.
  10. Simon Broome Familial Hyperlipidaemia Register Group and Scientific Steering Committee. Genetic causes of familial hypercholesterolaemia in patients in the UK: relation to plasma lipid levels and coronary heart disease risk. J Med Genet 2006
  11. [CrossRef] Timms KM, Wagner S, Samuels ME, Forbey K, Goldfine H, Jammulapati S, et al. A mutation in PCSK9 causing autosomal-dominant hypercholesterolemia in a Utah pedigree. Hum Genet 2004
  12. [CrossRef] Leren T. Mutations in the PCSK9 gene in Norwegian subjects w