Clinical Implications of MiR128, Angiotensin I Converting Enzyme and Vascular Endothelial Growth Factor Gene Abnormalities and Their Association with T2D

Imadeldin Elfaki; Rashid Mir; Faisel M Abu Duhier; Maeidh A Alotaibi; Adel Ibrahim Alalawy; Jameel Barnawi; Abdullatif Taha Babakr; Mohammad Muzaffar Mir; Faris Altayeb; Hyder Mirghani; Ehab A M Frah

doi:10.3390/cimb43030130

Clinical Implications of MiR128, Angiotensin I Converting Enzyme and Vascular Endothelial Growth Factor Gene Abnormalities and Their Association with T2D

Curr Issues Mol Biol. 2021 Nov 2;43(3):1859-1875. doi: 10.3390/cimb43030130.

Affiliations

¹ Department of Biochemistry, Faculty of Science, University of Tabuk, Tabuk 71491, Saudi Arabia.
² Prince and Fahd Bin Sultan Research Chair, Department of Medical Lab Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia.
³ King Faisal Medical Complex Laboratory, Ministry of Health, Taif 26521, Saudi Arabia.
⁴ Department of Medical Biochemistry, Faculty of Medicine, Umm Al-Qura University, Makkah 57039, Saudi Arabia.
⁵ Department of Basic Medical Sciences, College of Medicine, University of Bisha, Bisha 61992, Saudi Arabia.
⁶ Internal Medicine and Endocrine, Medical Department, Faculty of Medicine, University of Tabuk, Tabuk 71491, Saudi Arabia.
⁷ Department of Statistics, Faculty of Science, University of Tabuk, Tabuk 71491, Saudi Arabia.

Abstract

Type 2 DM (T2D) results from the interaction of the genetic and environmental risk factors. Vascular endothelial growth factor (VEGF), angiotensin I-converting enzyme (ACE), and MicroRNAs (MiRNAs) are involved in important physiological processes. Gene variations in VEGF, ACE and MiRNA genes are associated with diseases. In this study we investigated the associations of the VEGF-2578 C/A (rs699947), VEGF-2549 insertion/deletion (I/D), and ACE I/D rs4646994 and Mir128a (rs11888095) gene variations with T2D using the amplification refractory mutation system PCR (ARMS-PCR) and mutation specific PCR (MSP). We screened 122 T2D cases and 126 healthy controls (HCs) for the rs699947, and 133 T2D cases and 133 HCs for the VEGF I/D polymorphism. For the ACE I/D we screened 152 cases and 150 HCs, and we screened 129 cases and 112 HCs for the Mir128a (rs11888095). The results showed that the CA genotype of the VEGF rs699947 and D allele of the VEGF I/D polymorphisms were associated with T2D with OR =2.01, p-value = 0.011, and OR = 2.42, p-value = 0.010, respectively. The result indicated the D allele of the ACE ID was protective against T2D with OR = 0.10, p-value = 0.0001, whereas the TC genotype and the T allele of the Mir128a (rs11888095) were associated with increased risk to T2D with OR = 3.16, p-value = 0.0001, and OR = 1.68, p-value = 0.01, respectively. We conclude that the VEGF (rs699947), VEGF I/D and Mir128a (rs11888095) are potential risk loci for T2D, and that the D allele of the ACE ID polymorphism may be protective against T2D. These results help in identification and stratification for the individuals that at risk for T2D. However, future well-designed studies in different populations and with larger sample sizes are required. Moreover, studies to examine the effects of these polymorphisms on VEGF and ACE proteins are recommended.

Keywords: ACE I/D rs4646994; Mir128a (rs11888095); VEGF insertion and deletion (I/D); VEGF rs699947; genome wide association studies (GWAS); type 2 diabetes mellitus (T2D); vascular endothelial growth factor (VEGF).

MeSH terms

Alleles
Diabetes Mellitus, Type 2 / genetics*
Diabetes Mellitus, Type 2 / metabolism
Genetic Association Studies
Genetic Predisposition to Disease*
Genetic Variation*
Genotype
Humans
MicroRNAs / genetics*
Peptidyl-Dipeptidase A / genetics*
Polymorphism, Single Nucleotide
Vascular Endothelial Growth Factors / genetics*

Substances

MIRN128 microRNA, human
MicroRNAs
Vascular Endothelial Growth Factors
Peptidyl-Dipeptidase A

Grants and funding

0012-1441-S/University of Tabuk