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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 <i>VEGF</i>, <i>ACE</i> and <i>MiRNA</i> genes are associated with diseases. In this study we investigated the associations of the <i>VEGF</i>-2578 C/A (rs699947), <i>VEGF</i>-2549 insertion/deletion (I/D), and <i>ACE</i> I/D rs4646994 and <i>Mir128a</i> (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 <i>VEGF</i> 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 <i>Mir128a</i> (rs11888095). The results showed that the CA genotype of the VEGF rs699947 and D allele of the <i>VEGF</i> I/D polymorphisms were associated with T2D with OR =2.01, <i>p</i>-value = 0.011, and OR = 2.42, <i>p</i>-value = 0.010, respectively. The result indicated the D allele of the <i>ACE</i> ID was protective against T2D with OR = 0.10, <i>p</i>-value = 0.0001, whereas the TC genotype and the T allele of the <i>Mir128a</i> (rs11888095) were associated with increased risk to T2D with OR = 3.16, <i>p</i>-value = 0.0001, and OR = 1.68, <i>p</i>-value = 0.01, respectively. We conclude that the <i>VEGF</i> (rs699947), <i>VEGF</i> I/D and <i>Mir128a</i> (rs11888095) are potential risk loci for T2D, and that the D allele of the <i>ACE</i> 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.