Genotyping and Frequency of PCSK9 Variations Among Hypercholesterolemic and Diabetic Subjects

Edem Nuglozeh; Mohammad Feroze Fazaludeen; Nabil Hasona; Tarja Malm; Luisito B Mayor; Awdah Al-Hazmi; Ibraheem Ashankyty

doi:10.1007/s12291-018-0763-9

Genotyping and Frequency of PCSK9 Variations Among Hypercholesterolemic and Diabetic Subjects

Indian J Clin Biochem. 2019 Oct;34(4):444-450. doi: 10.1007/s12291-018-0763-9. Epub 2018 Jul 30.

Authors

Edem Nuglozeh^{1

2}, Mohammad Feroze Fazaludeen³, Nabil Hasona^{1

4}, Tarja Malm³, Luisito B Mayor⁵, Awdah Al-Hazmi¹, Ibraheem Ashankyty⁵

Affiliations

¹ 1Department of Biochemistry, College of Medicine, University of Hail, Hail, Kingdom of Saudi Arabia.
² 5Department of Biochemistry and Molecular Biology, College of Medicine, University of Hail, Hail, Kingdom of Saudi Arabia.
³ 3A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Neulaniementie 2, 70211 Kuopio, Finland.
⁴ 2Chemistry Department, Biochemistry Division, Faculty of Science, Beni-Suef University, Beni Suef, Egypt.
⁵ 4Department of Clinical Diagnostic, College of Applied Medical Sciences, University of Hail, Hail, Kingdom of Saudi Arabia.

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.

Keywords: Diabetes; Eucholesterolemia; Hypercholesterolemia; PCSK9; Single-nucleotide polymorphism.