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

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.

Correlation between the triglyceride-to-high-density lipoprotein cholesterol ratio and other unconventional lipid parameters with the risk of prediabetes and Type 2 diabetes in patients with coronary heart disease: a RCSCD-TCM study in China

“…However, abnormal blood glucose metabolism, including prediabetes (pre-DM) and DM, has become increasingly common; by 2045, more than 600 million people are estimated to develop pre-DM, and the same number will develop DM, according to the 2017 global estimates of DM prevalence and 2045 projections [ 6 ]. Besides, Asians are more prone to DM especially type 2 DM (T2DM) and other CHD complications, than Westerners due to various factors [ 7 ].…”

Interconnection between cardiovascular, renal and metabolic disorders: A narrative review with a focus on Japan

“…133,134 Similarly, genetic variation may play a role in differences in CVD complications of T2D between Asians and non-Asians. 135 Studies have shown various genotypes to be significantly associated with CVD in Asians with T2D, including Japanese, but not in Whites, including alleles encoding proteins involved in glucose and lipid metabolism. 135 Overall, the contribution of genetic variation to interethnic differences in CRM disease is a nascent field that is an important avenue for future research.…”

Signature pattern of gene expression and signaling pathway in premature diabetic patients uncover their correlation to early age coronary heart disease

“…Most CHD are thought to have a multifactorial genetic basis, involving genetic and environmental factors in interaction that determine a person's susceptibility to the disease [10][11][12]. Remarkably, many of the patients with CHD have multiple risk factors, including non-modifiable such as age and gender, and changeable risk factors such as hypertension and diabetes mellitus [13][14][15]. Although around 80% of CHD patients are attributable to the main modifiable risk factors, the differences between the ethnic groups could be due to genetic tendencies.…”