The Molecular Analysis of rs11614913 Polymorphism from miRNA196a Gene and Its Relationship with TNF-α Gene Expression in Cervical Cancer

Background: Cervical cancer (CC) is one of the most common malignant tumors in women, which has been diagnosed as fourth cancer in females worldwide. In addition to human papillomavirus (HPV), genetic factors, including altered expression of some microRNAs and mutations in tumor necrosis factor α (TNF-α) gene, are involved in this cancer. Objectives: This study aimed to investigate the rs11614913 polymorphism from the miRNA196a gene and its association with the expression of the TNF-α gene in cervical cancer for early diagnosis and treatment. Methods: In this study, 52 samples of pre-cancerous and cancerous lesions, and 50 tissue samples were collected from healthy subjects in an Iranian population. DNA was extracted from the samples, and rs11614913 polymorphism of the miRNA196a gene was investigated by PCR. RNA was extracted from the samples, and the expression of the miRNA196a and TNF-α genes were evaluated. Finally, for data analysis, Epi Info software version 7.1.3.10 and MedCalc Version 19.2.0 were used. Results: The frequency of CC, TC, and TT genotypes from rs11614913 polymorphism of miRNA196a gene was 0.58, 0.34, and 0.08, respectively, but in the healthy group it was 0.36, 0.46, and 0.18, respectively. The results also showed that the expression of miRNA196a and TNF-α genes in the patient group was higher than the control group. Conclusions: Based on the results of this study, a significant correlation was found between CC genotype and rs11614913 polymorphism of miRNA196a gene and TNF-α gene expression in the cervical cancer sample. Therefore, investigating these factors in patients with cervical cancer may be helpful.

Micro-RNA 196a2 expression and miR-196a2 (rs11614913) polymorphism in T1DM: a pilot study

Background Recent emerging evidence supports the role of miR-196a2 in various human diseases. However, its role in type 1 diabetes mellitus (T1DM) is still underestimated. We aimed, for the first time, to investigate the expression of miR-196a2 in T1DM and the association of miR-196a2 (rs11614913) polymorphism with susceptibility of T1DM in a sample of patients from Cairo, Egypt. Methods The study included 150 patients and 150 healthy subjects. Evaluation of rs11614913 genotypes and miR-196a2 expression was done using the allelic discrimination and quantitative reverse transcriptase polymerase chain reaction (PCR) method, respectively. Results The Hardy-Weinberg equilibrium of single nucleotide polymorphism(SNP) was detected among controls (p = 0.2). Our results revealed that the TT genotype was more frequent in patients (22.6%) than controls (10%) while the CC genotype was more frequent in controls (47.3%) than patients (39.3%) (p = 0.01). The frequency of the T allele was significantly higher in patients than in controls (41.7 vs. 31.3%), while the C allele was more frequent in controls (p = 0.008). After adjustment for traditional risk factors, the association of the TT genotype with T1DM remained significant (TT vs. CC, odds ration [OR] = 3.2, 95% confidence interval [CI]: 1.4–7.4, p = 0.005). Power analysis of the data yielded a statistical power of 80% for the miR-196a2 rs11614913 with T1DM. Relative expression of miR-196a2 showed significant decrease in patients compared to controls (median = 0.09, 0.5, interquartile range [IQR] = 0.03–1.6, 0.1–2.1). However, miR-196a2 expression showed no significant difference between different rs11614913 genotypes (p = 0.5). Conclusions Our findings demonstrated that miR-196a rs11614913 is associated with T1DM and decreased expression of miR-196a2 may play a role in pathogenesis of T1DM.

A passenger strand variant in miR-196a2 contributes to asthma severity in children and adolescents: A preliminary study

There is emerging evidence to support the role of microRNAs in allergic airway diseases and inflammation. Genetic variants in microRNA genes might affect microRNA-mediated cell regulation. This preliminary study was designed to investigate the association of the microRNA-196a2 rs11614913 (C/T) polymorphism with susceptibility to asthma and clinical outcomes in children and adolescents. Genotyping of rs11614913 polymorphism was determined in 96 patients with bronchial asthma (6–18 years of age) and 96 unrelated controls, using real-time polymerase chain reaction technology. In-silico target prediction and network core analyses were performed. The asthmatics did not show significant differences in genotype distribution (p = 0.609) and allele frequencies (p = 0.428) compared with the controls. There were also no associations with disease duration, age at onset, asthma phenotype, asthma control, therapeutic level, airway hyper-responsiveness, or biochemical parameters in the blood. However, the CC genotype was associated with a more severe degree of asthma (p = 0. 023) and higher frequency of nocturnal asthma (p = 0.002). Carriers for CC were 17 times more likely to develop nocturnal asthma, and had a more than 2.5-fold increased risk for poor disease outcome compared with CT and TT individuals. In conclusion, microRNA-196a2 rs11614913 polymorphism might be associated with asthma severity in our sample of the Egyptian population. Further investigations in studies with a larger sample size and functional tests are needed to validate our findings and to explore the detailed biological mechanisms.