Assessment of TNF-α (-857 C/T) gene polymorphism in oral lichen planus disease: A case-control study.

Background and aims: Oral lichen planus (OLP) is an inflammatory mucocutaneous disorder with an immune-mediated pathogenesis. The tumor necrosis factor-α (TNF-α) level in the serum of OLP patients is significantly higher than in the control group. TNF-α-857 C/T polymorphism can be related to the increased TNF-α level in blood circulation. This study investigated the relationship between TNF-α (-857 C/T) polymorphism and OLP patients in an Iranian population. Methods: Saliva samples were taken from 200 people, including 100 patients with OLP and 100 healthy people who did not have significant differences in age and sex. Then, DNA was extracted from them and the TNF-α (-857 C/T) genotype was identified using the polymerase chain reaction with confronting two-pair primers method. Statistical Package for the Social Sciences version 16 software analyzed the results. Results: The frequency of C/C, C/T, and T/T genotypes of the TNF-α-857 C/T polymorphism in the patient group were 78%, 18%, and 4%, respectively, and in the control group were 72%, 23%, and 5%, respectively. The differences between the two groups regarding allele (χ 2 = 0.97, p = 0.32) and genotype (χ 2 = 0.96, p = 0.62) frequency among the studied population were insignificant. Conclusion: This study showed that the difference in the frequency of single nucleotide polymorphism TNF-α-857 C/T polymorphism in the patient and control group had no significant relationship with the increased OLP incidence. Also, no significant association was observed between allele and genotype frequency of TNF-α (-857 C/T) with OLP subtypes.

Evaluation of the association between TNF-α-1031 T/C polymorphism with oral lichen planus disease.

BACKGROUND: Oral lichen planus (OLP) is a T-cell-mediated autoimmune disease that affects the epithelial cells of the oral cavity. This study was performed to investigate any possible relationship between - 1031(T/C) polymorphism (rs1799964) of the tumor necrosis factor α (TNF-α) gene with the risk and severity of oral lichen planus (OLP) disease among an Iranian population. METHOD: Saliva samples were collected from 100 patients with OLP and a similar number of healthy controls (age and sex-matched). Then, DNA was extracted from the collected samples for genotyping TNF-α-1031 T/C polymorphism using the PCR-CTPP method. The results were assessed using SPSS software. RESULTS: The findings revealed a significantly higher prevalence of the C allele in OLP patients (53%) compared to healthy controls (36%), suggesting an association between TNF-alpha gene polymorphism and OLP. A multivariate logistic regression analysis supported this finding, as the presence of the C allele was significantly associated with an increased risk of OLP [χ2 = 4.17, p = 0.04, 95% CI = 1.01-2.65, OR = 1.64]. However, our data indicated no significant association between TNF-alpha-1031 T/C gene polymorphism and OLP severity. CONCLUSIONS: These findings provide the first evidence supporting a possible role of TNF-α-1031 T/C gene polymorphism in OLP susceptibility in the Iranian population. The findings of this study demonstrate a positive association between TNF-α-1031 C/T allele distribution and the risk of OLP disease in the Iranian population. Therefore, carrying the C allele may increase the susceptibility to OLP disease.

Precision targeting of CuET overload to disrupt mitochondrial unfolded protein response by integrated liposome.

Mitochondria in breast cancer play a critical role in survival and adaptation to dynamic environments. Thus, targeting mitochondria emerges as a promising therapeutic strategy for breast cancer. However, the adaptive unfolded protein response in mitochondria (UPRmt) due to mitochondrial unspecific distribution might contribute to diminished therapeutic outcomes. Herein, mitochondrial targeting liposome agents (CTPP-Lipid) are constructed and adopted for delivering the copper ion (CuET-DSF), which is especially sensitive for mitochondria-abundant breast tumors. In brief, the CTPP-Lipid@CuET achieves the goal of Cu2+ overloading by mitochondria targeting delivery. This rapidly increases ROS production, disrupts mitochondrial structure, and avoids the adaptive UPRmt formation, finally leading to apoptosis of breast cancer cells. In general, the Cu2+ overloading at mitochondria by CTPP-Lipid@CuET is a potential strategy for antitumor therapy, providing new insights into breast tumor therapy.

An improved PCR-CTPP assay for the detection of ADH1B Arg48His polymorphism.

BACKGROUND: ADH1B Arg48His polymorphism is associated with the development of alcohol-related diseases. In this study, we aimed to explore an improved polymerase chain reaction with confronting two-pair primers (PCR-CTPP) assay for the detection of ADH1B Arg48His polymorphism. METHODS: A mismatch was introduced at the 3' end of each of the two allele-specific to increase the specificity of the reaction. But beyond that, a new mismatch at-3 positions of outer primers was designed to decrease the efficiency of the aforementioned primers and depresses the amplification of an internal nonspecific DNA control. A total of 180 samples from healthy volunteers Han Chinese were tested to evaluate this new assay. RESULTS: The protocol of PCR-CTPP was successful for genotyping of ADH1B Arg48His. The results from the improved PCR-CTPP assay were confirmed by Sanger sequencing, and correct genotyping rates were 100%.The genotype frequencies were 49.44% (89 cases) for His/His, 46.67% (84 cases) for Arg/His, and 3.89% (seven cases) for Arg/Arg respectively. CONCLUSIONS: This improved PCR-CTPP assay is simple, rapid, cost-effective, and reliable, specific for the detection of ADH1B Arg48His polymorphism in most clinical diagnostic laboratories.

A PCR method for VKORC1 G-1639A and CYP2C9 A1075C genotyping useful to warfarin therapy among Japanese.

Warfarin is widely prescribed for patients with the risk of thromboembolism around the world. The inter-individual and inter-racial differences in appropriate dosage depend highly on age, body weight, and genetic factors. A lot of studies including genome-wide association studies revealed that vitamin K epoxide reductase complex, subunit 1 (VKORC1) G-1639A and Cytochrome P450 (CYP) 2C9 A1075C are the most strong genetic factors for determining warfarin effects in Asians and Africans. Since we developed a quick and inexpensive genotyping method, polymerase chain reaction with confronting two-pair primers (PCR-CTPP), the method was applied for these genotypes to examine the possibility to clinical use. Subjects were 436 examinees (117 males and 319 females, aged 32 to 85 years) who attended a health checkup program in Japan. The PCR-CTPP for VKORC1 G-1639A and CYP2C9 A1075C was conducted for the subjects, as well as the samples genotyped by DigiTag2 method. The allele frequencies of VKORC1 G-1639A were 0.085 for G and 0.915 for A, and those of CYP2C9 A1075C were 0.979 for A and 0.021 for C, being in Hardy-Weinberg equilibrium (p = 0.658 and p = 0.514, respectively). These frequencies were similar to those reported in the HapMap project. Genotyping for both SNPs by PCR-CTPP was replicated by DigiTag2 method. Our results indicated that the PCR-CTPP could be one of the alternative methods for genotyping VKORC1 G-1639A and CYP2C9 A1075C for Asians and Africans with similar allele frequencies to Japanese.