MicroRNAs (miRNAs) are endogenous, small (18–23 nucleotides), non-coding RNA molecules. They regulate the posttranscriptional expression of their target genes. MiRNAs control vital physiological processes such as metabolism, development, differentiation, cell cycle and apoptosis. The control of the gene expression by miRNAs requires efficient binding between the miRNA and their target mRNAs. Genome-wide association studies (GWASs) have suggested the association of single-nucleotide polymorphisms (SNPs) with certain diseases in various populations. Gene polymorphisms of miRNA target sites have been implicated in diseases such as cancers, diabetes, cardiovascular and Parkinson’s disease. Likewise, gene polymorphisms of miRNAs have been reported to be associated with diseases. In this review, we discuss the SNPs in miRNA genes that have been associated with diabetes and atherosclerotic cardiovascular disease in different populations. We also discuss briefly the potential underlining mechanisms through which these SNPs increase the risk of developing these diseases.

Breast cancer is considered as one of the most aggressive types of cancer. Acquired therapeutic resistance is the major cause of chemotherapy failure in breast cancer patients. To overcome this resistance and to improve the efficacy of treatment, drug combination is employed as a promising approach for this purpose. The synergistic cytotoxic, apoptosis inducing, and cell cycle effects of the combination of LY294002 (LY), a phosphatidylinositide-3-kinase (PI3K) inhibitor, with the traditional cytotoxic anti-estrogen drug tamoxifen (TAM) in breast cancer cells (MCF-7) were investigated. LY and TAM exhibited potent cytotoxic effect on MCF-7 cells with IC₅₀ values 0.87 µM and 1.02 µM. The combination of non-toxic concentration of LY and TAM showed highly significant synergistic interaction as observed from isobologram (IC₅₀: 0.17 µM, combination index: 0.18, colony formation: 9.01%) compared to untreated control. The percentage of early/late apoptosis significantly increased after treatment of MCF-7 cells with LY and TAM combination: 40.3%/28.3% (p < 0.001), compared to LY single treatment (19.8%/11.4%) and TAM single treatment (32.4%/5.9%). In addition, LY and TAM combination induced the apoptotic genes Caspase-3, Caspase-7, and p53, as well as p21 as cell cycle promotor, and significantly downregulated the anti-apoptotic genes Bcl-2 and survivin. The cell cycle assay revealed that the combination induced apoptosis by increasing the pre-G₁: 28.3% compared to 1.6% of control. pAKT and Cyclin D1 protein expressions were significantly more downregulated by the combination treatment compared to the single drug treatment. The results suggested that the synergistic cytotoxic effect of LY and TAM is achieved by the induction of apoptosis and cell cycle arrest through cyclin D1, pAKT, caspases, and Bcl-2 signaling pathways.

Coronary artery disease (CAD) is a major cause of death all over the world. CAD is caused by atherosclerosis which is induced by the interaction of genetic factors and environmental factors. Traditional environmental risk factors include hyperlipidemia, diabetes mellitus, lack of exercise, obesity, poor diet and others. Genome-wide association studies have revealed the association of certain gene polymorphisms with susceptibility to CAD. Omentin 1 is an adipokine secreted by the visceral adipose tissues and has been reported to have anti-inflammatory, cardioprotective, and enhances insulin sensitivity. In this study, we examined the role of omentin-1 common single nucleotide polymorphisms (SNPs) (rs2274907 A>T and rs2274908 G>A) in CAD. We genotyped 100 CAD patients and 100 matched healthy controls from the south Indian population using an amplification refractory mutation system (ARMS-PCR) and allele-specific PCR (AS-PCR). Our result indicated the rs2274908 G>A is not associated with CAD. Results showed that there was a significant difference in rs2274907 A>T genotype distribution between controls and CAD cases (P-value < 0.05). Results indicated that the AT genotype of the rs2274907 is associated with CAD with OR = 3.0 (95% confidence interval (CI), 1.64 to 5.49), 1.65 (1.27 to 2.163), P = 0.002. The T allele of the rs2274907 was also associated with CAD with OR = 1.82 (95% CI, 1.193 to 2.80), 1.37 (1.08 to 1.74), P = 0.005. Rs2274907 genotype distribution was also correlated with serum total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), hypertension and diabetes. We conclude that the AT genotype and the T allele of the rs2274907 A>T is associated with Cad in the south Indian population. Further studies on the effect of the rs2274907 A>T on omentin-1 function are recommended, and future well-designed studies with larger sample sizes and in different populations are required to validate our findings.

Oxidative modification of low density lipoproteins (LDL) convert these native particles into pathogenic, immunogenic and atherogenic particles. Factors enhance LDL oxidation are poorly understood, especially in conditions of hyperglycemia. The present study was conducted to investigate which metabolic conditions are associated with the promotion of LDL oxidation in different glycemic situations. Adult male participants (274) were selected from patients admitted to the outpatient department of Diabetes Center in Al-Noor Specialized Hospital in Makkah and other citizens and residents in the city. The studied group was classified into three sub-groups: Group-I: control group of non-diabetic normal subjects, Group-II: subjects with impaired glucose tolerance (IGT) and Group-III: cases of type-2 diabetes mellitus (DM). Measurement of fasting blood glucose, 2 hour post-prandial blood glucose, glycosylated hemoglobin (HbA1c), triglycerides, serum cholesterol, HDL-cholesterol, LDL-cholesterol, ox-LDL, Total Antoxidant capacity (TAC) and Malondialdehyde (MDA) were performed. The obtained results were statistically analyzed. Oxidation of native LDL increase nearly two folds in Type-2 DM group compared to controls. There is also significant increase in Ox-LDL of IGT group compared to controls. The correlation between Ox-LDL concentration and HbA1c in the whole population of the study confirms the increased Ox-LDL in subjects with hyperglycemia. A negative correlation exists between the concentration of Ox-LDL and total antioxidant capacity (TAC) in each studied group and in the whole population of the study as well. A positive correlation also exists between Ox-LDL concentrations and LDL values, more clear in controls and Type-2 DM, while this correlation was not significant in IGT group. The ratio of LDL oxidation as expressed by ox-LDL/LDL was increased in IGT group compared to control. More significant increase was observed in type-2 DM group. We concluded that the concentration of Ox-LDL increased in subjects with type-2 DM and IGT compared to controls. Moreover, oxidation of native LDL was associated with low levels of TAC and positively correlated with LDL levels, total cholesterol, HbA1c, body mass index (BMI) and increased age.