Pharmacogenetic Approach for the Prevention of Rivaroxaban's ADRs: A Systematic Review and Meta-Analysis.

Introduction: Pharmacogenetics is a potential approach that can be applied to decline the burden of rivaroxaban's ADRs. The current systematic review and meta-analysis aim to identify genetic variants correlated with rivaroxaban exposure and evaluate their importance. Methods: We systematically searched PubMed, Web of Science, and Scopus databases for all observational and interventional studies. The fixed effect method was used to pool the data when the Q-test's p value was higher than 0.1. We used random models when the p value was less than 0.1. Results: Data from ten studies (4721 participants) were analyzed in the current review. Qualitative synthesis from included studies found that two variants of ABCB1 (rs1045642 and rs2032582) and one variant of APOB (rs13306198) are potential contributors to rivaroxaban concentrations. Both wild homozygotes (AA) and heterozygotes (AC) of rs1045642 have significantly lower rivaroxaban concentrations compared to mutated homozygotes (CC) (SMD = 0.516, 95% CI: 0.115 to 0.917; SMD = 0.772, 95% CI: 0.088 to 1.455, respectively). Nevertheless, pooling unadjusted odds ratios did not yield a statistically significant correlation between rivaroxaban ADRs and genetic mutations. Conclusion: This study revealed that being an AC or CC for rs1045642 is attributed to a considerably higher rivaroxaban level in participants using rivaroxaban. That is to say, rs1045642 is a remarkable predictor of rivaroxaban metabolism. We concluded that identifying rs1045642 before drug administration might decrease ADRs although further studies adjusted for potential confounders are strongly suggested.

Investigation of the relationship between monocyte chemoattractant protein 1 rs1024611 variant and severity of COVID-19.

BACKGROUND: Higher expression of Monocyte Chemoattractant Protein 1 (MCP-1) was reported in several studies. The clinical severity of Coronavirus disease 2019 (COVID-19) could be affected by genetic polymorphisms in MCP-1. This study aimed to examine the impact of MCP-1 2518A/G polymorphism and clinical parameters with COVID-19 severity. METHODS: The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for MCP-1 rs1024611 (A/G) genotyping in 116 outpatients, hospitalized, and ICU patients. The biochemical and hematological profiles were collected from the patient's medical records. RESULTS: Based on the statistical analysis, there was no significant relationship between the -2518A/G (rs1024611) genetic polymorphism in the regulatory region of the MCP-1 gene and the severity of the COVID-19. Multivariate logistic regression analysis has shown that the severity of COVID-19 infection was associated with decreased levels of eosinophils, neutrophils, lymphocytes, and, monocyte and higher levels of SGPT, SGOT, NLR, CRP, ferritin, urea, and D-Dimer (P < 0.05). CONCLUSION: The MCP-1 gene polymorphism had no impact on COVID-19 severity. However, to confirm these results, a large-scale study needs to be conducted.

Evaluation of the association between clinical parameters and ADAM33 and ORMDL3 asthma gene single-nucleotide polymorphisms with the severity of COVID-19.

BACKGROUND: Coronavirus Disease of 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients had varying clinical symptoms and disease severity (mild, moderate, severe, and critical). Several risk factors, including genetic polymorphisms, have been reported to be associated with disease risk and severity. This study aimed to investigate the association of two polymorphisms in the orosomucoid1-like 3 (ORMDL3) and a disintegrin and metalloprotease 33 (ADAM33) asthma-related genes with the severity of COVID-19. MATERIAL AND METHODS: The study included 116 COVID-19 patients with a positive polymerase chain reaction (PCR) test for the SARS-CoV-2 Delta variant. 58 patients with moderate symptoms, 28 patients with severe symptoms, and 30 outpatients with mild symptoms. Genotyping of rs7216389 in the ORMDL3 and rs2280091 in ADAM33 genes was performed by polymerase chain reaction-restriction fragment length polymorphism. Furthermore, records of patients were studied for hematological profiles and biochemical markers. RESULTS: No significant association was found between rs7216389 and rs2280091 and the severity of COVID-19 between different groups of COVID-19 patients. The serum levels of RBC and neutrophil-to-lymphocyte ratio were significantly increased; the erythrocyte sedimentation rate (ESR), and Aspartate transaminase (SGOT) were significantly decreased during treatment in intensive care unit (ICU) patients. The serum levels of red blood cells, Platelets, Urea, Alkaline phosphatase, ESR, Alanine transaminase (SGPT), and SGOT were significantly increased during treatment in hospitalized patients. The serum levels of inflammatory factors, including C-reactive protein (CRP), D-dimer, and Ferritin at the time of admission, were significantly higher in patients admitted to the ICU patients compared to the other group of patients. CONCLUSION: The two polymorphisms studied in this research are not suitable markers for predicting the severity of COVID-19. However, there are significant differences in the amounts of some blood factors in different groups of COVID-19 patients (P < 0.05) and these factors can be used as a marker for the disease severity prediction.

The effect of CHRNA3 rs1051730 C>T and ABCB1 rs3842 A>G polymorphisms on non-small cell lung cancer and nicotine dependence in Iranian population.

AIMS: Lung cancer is still the leading cause of cancer mortality in all over the world. Nicotine and its derivatives are the most well-known carcinogens that participate in both etiology and progression of lung cancer. The objective of the current study was to investigate whether single nucleotide polymorphisms (SNPs) rs1051730C > T in CHRNA3 and rs3842A > G in ABCB1, two genes contributing in the mechanism of disposition and metabolism of nicotine and its derivatives, could modify the risk of developing lung cancer, as well as nicotine dependence in Iranian. MAIN METHODS: The genotyping analysis for these two SNPs was conducted in a case-control study of 108 lung cancer cases and 120 healthy controls using ARMS-PCR and Tetra-primer ARMS-PCR techniques. The correlation between studied SNPs and lung cancer was assessed by the regression analysis. KEY FINDINGS: We observed a significant association between lung cancer and rs1051730C > T by using four genetic models: allele (OR:1.83; 95% CI:1.24-2.6; p = 0.002), dominant (OR: 2.19; 95% CI:1.27-3.78; p = 0.005), recessive (OR: 2.25; 95% CI: 1.02-4.95; p = 0.043) and additive (TT vs CC: OR:3.25; 95% CI:1.38-7.60; p = 0.007, CT vs CC: OR:1.96; 95% CI:1.10-3.48; p = 0.021). Furthermore, a significant association between this variant and nicotine dependence (OR: 2.27; 95% CI: 1.52-3.39; p = 0.00005) was reported. However, no association was found for rs3842A > G. SIGNIFICANCE: The results suggested that the CHRNA3 rs1051730C > T via a smoking-dependent manner could modify susceptibility to lung cancer among Iranian population.

Relationship between weight gain and survival rate in patients with metastatic lung cancer.

Background: Lung cancer accounts for about 13% of all cancers and about 60% of patients with lung cancer also experience weight loss during treatment. There seems to be a clear correlation between the therapeutic outcomes of patients based on their weight changes during treatment. The aim of this study was to investigate the relationship between weight changes during and after treatment and the therapeutic outcomes of a patient with metastatic lung cancer. Methods: This cohort study was performed on patients with the diagnosis of non-surgical metastatic lung cancer referred to Hematology and Oncology Clinic, Rasoul-e-Akram Hospital. Patients were divided into two groups with a weight gain of more than 5% and a weight gain of 5% and less. The information was entered into the SPSS version 21 software. In the descriptive analysis, mean and standard deviation (SD) were used. To compare quantitative variables, independent samples t-test, Mann-Whitney, chi-square or Fisher exact tests were used to compare qualitative variables and correlation test was used to determine the correlation between quantitative data. Survival curves were used to show differences in two groups of studies. A regression model was used to calculate the hazard ratio. The significance level was less than 0.05. Results: Sixty patients, including 40 males (66.7%) and 20 females (33.3%) were studied. The mean age of patients was 62.22±9.00 years (43-83 years). The mean weight changes in the patients were -1.28±6.11 kg (-16 to 16kg). Forty-seven patients (78.3%) had weight gain less than 5%. There was no significant difference in overall survival (OS) and progression-free survival (PFS) according to weight gain. Conclusion: Finally, the findings of the study showed that, despite the fact that PFS and OS in the weight gain group were greater than 5% of the original weight; the difference was not statistically significant.

The Role of Dihydropyrimidine Dehydrogenase and Thymidylate Synthase Polymorphisms in Fluoropyrimidine-Based Cancer Chemotherapy in an Iranian Population.

BACKGROUND: The fluoropyrimidine drug 5-Fluorouracil (5-FU) and the prodrug capecitabine have been extensively used for treatment of many types of cancer including colorectal, gastric, head and neck. Approximately, 10 to 25% of patients suffer from severe fluoropyrimidine-induced toxicity. This may lead to dose reduction and treatment discontinuation. Pharmacogenetics research could be useful for the identification of predictive markers in chemotherapy treatment. The aim of the study was to investigate the role of five genetic polymorphisms within two genes (DPYD, TYMS) in toxicity and efficacy of fluoropyrimidine-based chemotherapy. METHODS: Total genomic DNA was extracted from 83 cancer patients treated with fluoropyrimidine-based chemotherapy. In this study, three polymorphisms were genotyped in dihydropyrimidine dehydrogenase gene c.1905+1 G>A (DPYD*2A; rs3918290), c.1679 T>G (I560S; DPYD*13; rs55886062), and c.2846A>T (D949V; rs67376798) and two polymorphisms, besides the Variable Number of Tandem Repeat (VNTR) polymorphism and 6-bp insertion/deletion polymorphism in thymidylate synthase gene. The analysis of polymorphisms for rs3918290, rs55886062, rs67376798 and 6-bp insertion/deletion in TYMS was done by Polymerase Chain Reaction-restriction Fragment Length Polymorphism (PCRRFLP) TYMS VNTR analysis. 5-FU-related toxicities such as anemia, febrile neutropenia, neurotoxicity, vomiting, nausea, and mucositis were evaluated according to NCI-CTC criteria version 4.0. T-test and chi-square were used and p-values less than 0.05 were considered statistically significant. RESULTS: DPYD gene polymorphisms were not observed in this study. The frequency of the TYMS +6 bp allele was 40.35% and the -6 bp allele was 59.65% in this study. The frequency of VNTR 2R allele was 48.75% and 3R allele was 51.15%. Toxicity grade II diarrhea, mucositis, nausea, vomiting, and neurotoxicity was 2.2, 24.1, 15.7, 6, and 51.8%, respectively. Thymidylate synthase ins/del polymorphisms were associated with increased grade III neurotoxicity (p=0.02). Furthermore, anemia grade III was significantly associated with 2R/2R genotype (0.009). CONCLUSION: Thymidylate synthase gene polymorphisms may play a key role in fluoropyrimidne -based chemotherapy. Although rare DPYD polymorphisms were not observed in our study, according to large population studies, DPYD gene polymorphisms could be used as a predictive biomarker for patient treatments.

The effect of relaxation techniques on edema, anxiety and depression in post-mastectomy lymphedema patients undergoing comprehensive decongestive therapy: A clinical trial.

OBJECTIVES: Lymphedema is sometimes accompanied by high degrees of anxiety and depression. This study aimed to assess the effects of relaxation techniques on the level of edema, anxiety and depression in women undergoing Comprehensive Decongestive Therapy (CDT). DESIGN: This clinical trial compared two treatment methods in 31 women with post-mastectomy lymphedema, including 15 cases who received CDT and 16 who received RCDT (Relaxation plus CDT). The edema volume, anxiety and depression scores were compared at the first and last sessions of the first phase of the treatment and six weeks afterwards. RESULTS: The edema, anxiety and depression scores were 63.6%, 54.1% and 65.5% in the RCDT group and 60.7%, 31.4% and 35.2% in the CDT group. There were significant differences between the two groups in terms of the reduction in depression (p = 0.024) and anxiety (p = 0.011) scores throughout the study. This significant relationship was due to the differences in the depression score in the 3rd and 9th weeks of the study between the two groups. Similarly, anxiety levels differed significantly between the two groups at the 9th week of the study (P = 0.013). CONCLUSION: Relaxation techniques reduced the anxiety and depression scores and the volume of edema in the patients with lymphedema. The addition of this intervention to the therapeutic package for lymphedema patients requires further studies in terms of cost-effectiveness.