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

Rano Alieva1, Aleksandr Shek1, Alisher Abdullaev2

  • 1CAD & Atherosclerosis Department, Republican Specialized Center of Cardiology, Tashkent, Uzbekistan.

Frontiers in Clinical Diabetes and Healthcare
|November 29, 2023
PubMed

Insights

The G allele of the PCSK9 E670G gene is linked to a higher risk of type 2 diabetes mellitus (T2DM) in patients with coronary artery disease (CAD), especially those with heterozygous familial hypercholesterolemia (HeFH). This finding is significant for understanding genetic predispositions in cardiovascular disease patients.

Area of Science:

  • Genetics
  • Cardiology
  • Endocrinology

Background:

  • Coronary Artery Disease (CAD) and Heterozygous Familial Hypercholesterolemia (HeFH) are significant cardiovascular conditions.
  • The role of PCSK9 genetic variations in disease development, particularly with co-occurring Type 2 Diabetes Mellitus (T2DM), requires further investigation.

Purpose of the Study:

  • To evaluate the distribution of the PCSK9 E670G genetic polymorphism and PCSK9 levels in patients with CAD and HeFH.
  • To determine the association of these factors with the presence of T2DM in the Uzbek population.

Main Methods:

  • Genotyping of the PCSK9 E670G (rs505151) polymorphism using PCR-RFLP in 201 CAD patients (including 57 with HeFH).
  • Assessment of PCSK9 levels and diagnosis of HeFH using DLCN criteria.
  • Statistical analysis to compare genotype frequencies, allele distributions, and clinical outcomes.

Main Results:

  • The G allele of PCSK9 E670G was more frequent in HeFH patients compared to non-HeFH patients and controls, though not statistically significant.
  • PCSK9 levels were higher in HeFH patients compared to non-HeFH patients not on statins.
  • Carriers of AG+GG genotypes in the HeFH group showed a significantly higher risk of T2DM (RR 4.18), myocardial infarction (RR 1.79), and revascularization (RR 12.6).
  • T2DM was also more common among G allele carriers in patients with non-HeFH (RR 1.85).

Conclusions:

  • The "gain-of-function" G allele of the PCSK9 E670G polymorphism is significantly associated with a higher prevalence of T2DM in patients with CAD, both with and without HeFH, within the Uzbek population.
Abstract

Keywords:
CADUzbek populationheterozygous familial hypercholesterolemiapcsk9type 2 diabetes mellitus

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