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Genotyping and Frequency of PCSK9 Variations Among Hypercholesterolemic and Diabetic Subjects

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Indian Journal of Clinical Biochemistry Aims and scope Submit manuscript

Abstract

Non-synonymous single-nucleotide polymorphism (SNPs) in the gene for proprotein convertase subtilisin/kexin type 9 (PCSK9) can influence cholesterol and glucose metabolism, leading to increased risk of cardiovascular disease and diabetes. To determine the frequency of four common PCSK9 SNPs, L10Ins, A56V, I474V, and E670G, in a population sample (n = 98) of the Hail region of Kingdom of Saudi Arabia. Blood was collected from participants; serum cholesterol, blood glucose and glycated hemoglobin were determined; genomic DNA was extracted and PCR amplicons from SNP-containing PCSK9 exons were subjected to Sanger sequencing. Out of 98 participants. 10 (10.20%) carried none of the SNPs, 2 (2.04%) the L10ins/A56V linked SNPs, 35 (35.71%) the I474V SNP, 22 (22.45%) both the I474V and E670G SNPs, and 29 (29.59%) the E670G SNP. Of the 30 eucholesterolemic diabetics patients, 11 (36.66%) carried the I474V SNP, 10 (33.33%) the E679G SNP and 6 (20%) the I474V/E679G. SNPs. Of 63 diabetic patients, 26 (41.26%) carry I474V SNP and 22 (34.92%) carry E670G SNP. Our data demonstrated that the I474V and E670G PCSK9 variants are very frequent in the Hail region of Saudi Arabia and are found at even higher frequency among diabetics. Further investigations are needed to determine whether these variations or another variant segregating with them can explain its apparent association with diabetes in this population.

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Abbreviations

ADH:

Autosomal dominant hypercholesterolemia

CAD:

Coronary artery disease

GOF:

Gain of function

LDL-C:

Low-density lipoprotein-cholesterol

LDLR:

Low-density lipoprotein receptor

LOF:

Loss of function

PCSK9:

Proprotein convertase subtilisin/kexin type 9

SNP:

Single-nucleotide polymorphism

FBG:

Fasting blood glucose

HbA1c:

Glycated hemoglobin

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Acknowledgements

This research was funded by UOH. The authors thank Prof Majambu Mbikay of the Ottawa Hospital Research Institute for his critical review this manuscript before its submission.

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Authors and Affiliations

  1. Department of Biochemistry, College of Medicine, University of Hail, Hail, Kingdom of Saudi Arabia

    Edem Nuglozeh, Nabil Hasona & Awdah Al-Hazmi

  2. Chemistry Department, Biochemistry Division, Faculty of Science, Beni-Suef University, Beni Suef, Egypt

    Nabil Hasona

  3. A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Neulaniementie 2, 70211, Kuopio, Finland

    Mohammad Feroze Fazaludeen & Tarja Malm

  4. Department of Clinical Diagnostic, College of Applied Medical Sciences, University of Hail, Hail, Kingdom of Saudi Arabia

    Luisito B. Mayor & Ibraheem Ashankyty

  5. Department of Biochemistry and Molecular Biology, College of Medicine, University of Hail, Hail, Kingdom of Saudi Arabia

    Edem Nuglozeh

Authors
  1. Edem Nuglozeh
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  2. Mohammad Feroze Fazaludeen
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Correspondence to Edem Nuglozeh.

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Nuglozeh, E., Fazaludeen, M.F., Hasona, N. et al. Genotyping and Frequency of PCSK9 Variations Among Hypercholesterolemic and Diabetic Subjects. Ind J Clin Biochem 34, 444–450 (2019). https://doi.org/10.1007/s12291-018-0763-9

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  • DOI: https://doi.org/10.1007/s12291-018-0763-9

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