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Review
. 2022 Jan 6;19(2):647.
doi: 10.3390/ijerph19020647.

Coronary Heart Disease in Type 2 Diabetes Mellitus: Genetic Factors and Their Mechanisms, Gene-Gene, and Gene-Environment Interactions in the Asian Populations

Khairul Anwar Zarkasi  1   2 , Nor Azian Abdul Murad  1 , Norfazilah Ahmad  3 , Rahman Jamal  1 , Noraidatulakma Abdullah  1   4
Affiliations
Review

Coronary Heart Disease in Type 2 Diabetes Mellitus: Genetic Factors and Their Mechanisms, Gene-Gene, and Gene-Environment Interactions in the Asian Populations

Khairul Anwar Zarkasi et al. Int J Environ Res Public Health. .

Abstract

Asians are more susceptible to type 2 diabetes mellitus (T2D) and its coronary heart disease (CHD) complications than the Western populations, possibly due to genetic factors, higher degrees of obesity, insulin resistance, and endothelial dysfunction that could occur even in healthy individuals. The genetic factors and their mechanisms, along with gene-gene and gene-environment interactions associated with CHD in T2D Asians, are yet to be explored. Therefore, the objectives of this paper were to review the current evidence of genetic factors for CHD, summarize the proposed mechanisms of these genes and how they may associate with CHD risk, and review the gene-gene and gene-environment interactions in T2D Asians with CHD. The genetic factors can be grouped according to their involvement in the energy and lipoprotein metabolism, vascular and endothelial pathology, antioxidation, cell cycle regulation, DNA damage repair, hormonal regulation of glucose metabolism, as well as cytoskeletal function and intracellular transport. Meanwhile, interactions between single nucleotide polymorphisms (SNPs) from different genes, SNPs within a single gene, and genetic interaction with environmental factors including obesity, smoking habit, and hyperlipidemia could modify the gene's effect on the disease risk. Collectively, these factors illustrate the complexities of CHD in T2D, specifically among Asians.

Keywords: coronary heart disease; gene-environment interaction; gene-gene interaction; type 2 diabetes mellitus.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Proposed mechanisms of genes related to energy and lipoprotein metabolisms associated with CHD in the T2D Asian population. * Significant association with CHD exclusive in T2D Asians but not T2D Caucasians. Abbreviations: AMPK (5′ adenosine monophosphate-activated protein kinase), ERK (extracellular signal-regulated kinase), LDL (low-density lipoprotein), PPAR (peroxisome proliferation-activated receptor).
Figure 2
Figure 2
Proposed mechanisms of genes related to vascular and endothelial pathology associated with CHD in the T2D Asian population. * Significant association with CHD exclusive in T2D Asians but not T2D Caucasians. Abbreviations: eNOS (endothelial nitric oxide synthase), VSMCs (vascular smooth muscle cells).
Figure 3
Figure 3
Proposed mechanisms of genes related to antioxidation mechanisms associated with CHD in the T2D Asian population. * Significant association with CHD exclusive in T2D Asians but not T2D Caucasians. Abbreviations: CoQ10 (coenzymeQ10 or ubiquinone), ETC (electron transport chain).
See this image and copyright information in PMC

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