Behçet's disease (BD) is a chronic inflammatory autoimmune disease. Although raised levels of proinflammatory cytokines in BD have been reported, the pathogenesis is still unknown. The aim of this study was to investigate the association of NFKB1 and NFKBIA polymorphisms and their single and combined analysis effects on susceptibility of BD in Turkish population. We analysed the distribution of NFKB1 ‐94 ins/del ATTG (rs28362491) and NFKBIA 3′ UTR A→G (rs696) polymorphisms using PCR‐RFLP method in 89 patients with BD and 190 controls in this population. Statistical analysis of the results was performed by calculating OR, and 95% CI via χ2 test and using Bonferroni correction. According to the significant results of both single and combined genotype analysis, the frequencies of ins/ins genotype and ins allele of rs28362491 were significantly higher in patients with BD (Pc = 0.003, 0.004, respectively). Also, higher frequencies of the rs696 variant containing AA genotype was found in patients with BD (Pc = 0.0033), whereas no statistical significant differences in distribution of the alleles of rs696 polymorphism in patients and controls. In addition, according to the combined genotype analysis, the wild type of both rs28362491 and rs696 polymorphisms (ins/ins/AA genotype) was also significantly higher in BD cases (Pc = 0.044). Our findings prove that both single and combined genotype analysis of rs28362491 and rs696 polymorphisms indicate that the wild genotypes of both two SNPs (ins/ins and AA genotypes) and ins/ins/AA combined genotype are strongly associated with enhanced risk of BD in a Turkish population.
30 April 2021 in TURKISH JOURNAL OF MEDICAL SCIENCES
In the present study we aimed to figure out the effect of metformin on the expression of AMPK-alpha, cyclin D1 and Tp53, and apoptosis in primary breast cancer cells (PBCCs). PBCCs were treated with two doses of metformin (0 mM, 25 mM). Proliferation was determined by BrdU assay. Real-time PCR was used to assess AMPK-alpha, cyclin D1, and Tp53 gene expressions; apoptotic indexes of PBCCs were analyzed using flow cytometry. 24 hour-incubation with 25 mM metformin reduced the proliferation of PBCCs. AMPK-alpha gene expression in PBCCs was not affected by 25 mM metformin treatment compared with the control group. PBCCs treated with 25 mM metformin had lower cyclin D1 expression compared with non-treated cells, however, the difference was not statistically significant. 25mM dose of metformin increased p53 expression significantly compared with the non-treated group. The high concentration of metformin elevated the number of Annexin V positive apoptotic cells, and the increase in the apoptotic index was statistically significant. Metformin can modulate cyclin D1 and p53 expression through AMPK-alpha independent mechanism in breast cancer cells, leading to cell proliferation inhibition and apoptosis induction.