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E670G PCSK9 polymorphism in HeFH & CAD with diabetes: is the bridge to personalized therapy within reach?

OBJECTIVE: To assess the distribution of PCSK9 E670G genetic polymorphism and PCSK9 levels in patients with Coronary Artery Disease (CAD) and Heterozygous Familial Hypercholesterolemia (HeFH), based on the presence of type 2 Diabetes Mellitus (T2DM). METHODS: The study included 201 patients with chr...

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Autores principales: Alieva, Rano, Shek, Aleksandr, Abdullaev, Alisher, Fozilov, Khurshid, Khoshimov, Shovkat, Abdullaeva, Guzal, Zakirova, Dariya, Kurbanova, Rano, Kan, Lilia, Kim, Andrey
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10646404/
https://www.ncbi.nlm.nih.gov/pubmed/38028979
http://dx.doi.org/10.3389/fcdhc.2023.1277288
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author Alieva, Rano
Shek, Aleksandr
Abdullaev, Alisher
Fozilov, Khurshid
Khoshimov, Shovkat
Abdullaeva, Guzal
Zakirova, Dariya
Kurbanova, Rano
Kan, Lilia
Kim, Andrey
author_facet Alieva, Rano
Shek, Aleksandr
Abdullaev, Alisher
Fozilov, Khurshid
Khoshimov, Shovkat
Abdullaeva, Guzal
Zakirova, Dariya
Kurbanova, Rano
Kan, Lilia
Kim, Andrey
author_sort Alieva, Rano
collection PubMed
description OBJECTIVE: To assess the distribution of PCSK9 E670G genetic polymorphism and PCSK9 levels in patients with Coronary Artery Disease (CAD) and Heterozygous Familial Hypercholesterolemia (HeFH), based on the presence of type 2 Diabetes Mellitus (T2DM). METHODS: The study included 201 patients with chronic CAD, including those with HeFH (n=57, group I) and without it (n=144, group II). DLCN was used to diagnose HeFH. The PCSK9 E670G (rs505151) polymorphism was genetically typed using the PCR-RFLP procedure. In both the patient and control groups, the genotype frequency matched the Hardy-Weinberg equilibrium distribution (P>0.05). RESULTS: There were twice more G alleles in group I (13, 11.4%) than in group II (17, 6.0%), and thrice more (1, 3.0%) than in the healthy control group; nevertheless, these differences weren’t statistically significant. Simultaneously, PCSK9 levels were higher in HeFH patients (P<0.05) compared to non-HeFH patients not taking statins (n=63). T2DM was equally represented in groups I and II (31.6% vs. 33.3%). But carriers of AG+GG genotypes in group I had a higher chance of having a history of T2DM (RR 4.18; 95%CI 2.19-8.0; P<0.001), myocardial infarction (RR 1.79; 95%CI 1.18-2.73; P<0.05), and revascularization (RR 12.6; 95%CI 4.06-38.8; P<0.01), than AA carriers. T2DM was also more common among G allele carriers (RR 1.85; 95% CI 1.11-3.06; P<0.05) in patients with non-HeFH. CONCLUSION: T2DM in patients with CAD, both with HeFH and non-HeFH, in the Uzbek population was significantly more often associated with the presence of the “gain-of-function” G allele of the PCSK9 E670G genetic polymorphism.
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spelling pubmed-106464042023-11-01 E670G PCSK9 polymorphism in HeFH & CAD with diabetes: is the bridge to personalized therapy within reach? Alieva, Rano Shek, Aleksandr Abdullaev, Alisher Fozilov, Khurshid Khoshimov, Shovkat Abdullaeva, Guzal Zakirova, Dariya Kurbanova, Rano Kan, Lilia Kim, Andrey Front Clin Diabetes Healthc Clinical Diabetes and Healthcare OBJECTIVE: To assess the distribution of PCSK9 E670G genetic polymorphism and PCSK9 levels in patients with Coronary Artery Disease (CAD) and Heterozygous Familial Hypercholesterolemia (HeFH), based on the presence of type 2 Diabetes Mellitus (T2DM). METHODS: The study included 201 patients with chronic CAD, including those with HeFH (n=57, group I) and without it (n=144, group II). DLCN was used to diagnose HeFH. The PCSK9 E670G (rs505151) polymorphism was genetically typed using the PCR-RFLP procedure. In both the patient and control groups, the genotype frequency matched the Hardy-Weinberg equilibrium distribution (P>0.05). RESULTS: There were twice more G alleles in group I (13, 11.4%) than in group II (17, 6.0%), and thrice more (1, 3.0%) than in the healthy control group; nevertheless, these differences weren’t statistically significant. Simultaneously, PCSK9 levels were higher in HeFH patients (P<0.05) compared to non-HeFH patients not taking statins (n=63). T2DM was equally represented in groups I and II (31.6% vs. 33.3%). But carriers of AG+GG genotypes in group I had a higher chance of having a history of T2DM (RR 4.18; 95%CI 2.19-8.0; P<0.001), myocardial infarction (RR 1.79; 95%CI 1.18-2.73; P<0.05), and revascularization (RR 12.6; 95%CI 4.06-38.8; P<0.01), than AA carriers. T2DM was also more common among G allele carriers (RR 1.85; 95% CI 1.11-3.06; P<0.05) in patients with non-HeFH. CONCLUSION: T2DM in patients with CAD, both with HeFH and non-HeFH, in the Uzbek population was significantly more often associated with the presence of the “gain-of-function” G allele of the PCSK9 E670G genetic polymorphism. Frontiers Media S.A. 2023-11-01 /pmc/articles/PMC10646404/ /pubmed/38028979 http://dx.doi.org/10.3389/fcdhc.2023.1277288 Text en Copyright © 2023 Alieva, Shek, Abdullaev, Fozilov, Khoshimov, Abdullaeva, Zakirova, Kurbanova, Kan and Kim https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Clinical Diabetes and Healthcare
Alieva, Rano
Shek, Aleksandr
Abdullaev, Alisher
Fozilov, Khurshid
Khoshimov, Shovkat
Abdullaeva, Guzal
Zakirova, Dariya
Kurbanova, Rano
Kan, Lilia
Kim, Andrey
E670G PCSK9 polymorphism in HeFH & CAD with diabetes: is the bridge to personalized therapy within reach?
title E670G PCSK9 polymorphism in HeFH & CAD with diabetes: is the bridge to personalized therapy within reach?
title_full E670G PCSK9 polymorphism in HeFH & CAD with diabetes: is the bridge to personalized therapy within reach?
title_fullStr E670G PCSK9 polymorphism in HeFH & CAD with diabetes: is the bridge to personalized therapy within reach?
title_full_unstemmed E670G PCSK9 polymorphism in HeFH & CAD with diabetes: is the bridge to personalized therapy within reach?
title_short E670G PCSK9 polymorphism in HeFH & CAD with diabetes: is the bridge to personalized therapy within reach?
title_sort e670g pcsk9 polymorphism in hefh & cad with diabetes: is the bridge to personalized therapy within reach?
topic Clinical Diabetes and Healthcare
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10646404/
https://www.ncbi.nlm.nih.gov/pubmed/38028979
http://dx.doi.org/10.3389/fcdhc.2023.1277288
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