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INTRODUCTION: Exposure to biomass smoke, cigarettes, alcohol, and the impairment of immunoregulation are considered to be risk factors for tuberculosis. Tumour necrosis factor (TNF) -308G/A and -238G/A gene polymorphisms have been associated with tuberculosis. However, the results remain inconsistent. The aim of this study was to determine the association between TNF polymorphisms and tuberculosis in the presence of biomass smoke, cigarettes, and alcohol in a Mexican population. MATERIAL AND METHODS: TNF polymorphisms were determined in 118 tuberculosis patients and 223 controls. We performed a univariate, bivariate, stratified analysis. Odds ratios, confidence intervals, and p-values were calculated. RESULTS: Occupational biomass smoke exposure was associated with tuberculosis between the patients and controls (OR = 1.70, 95% CI: 1.08-2.70, p = 0.02). We also found an association of the -308A allele carriers between the patients and controls without exposure to occupational (p = 0.04, OR = 0.16, 95% CI: 0.01-0.92) and in-home (p = 0.02, OR = 0.14, 95% CI: 0.01-0.81) biomass smoke, as well as an association with alcohol (p = 0.01, OR = 0.24, 95% CI: 0.05-0.75). The haplotype analysis revealed an association of the -308A/-238G haplotype between patients and nonconsanguineous controls without exposure to occupational (p = 0.02, OR = 0.12, 95% CI: 0.01-0.99) and in-home (p = 0.01, OR = 0.1, 95% CI: 0.01-0.9) biomass smoke, cigarette use (p = 0.04, OR = 0.28, 95% CI: 0.08-0.98), and alcohol (p = 0.02, OR = 0.22, 95% CI: 0.05-0.88) intake. CONCLUSIONS: The TNF -308A allele and the -308A/-238G haplotype are associated with tuberculosis, as are exposure to biomass smoke, cigarettes, and alcohol. No association for the -238G/A polymorphism was found. Our results provide insight into a possible protective role of TNF polymorphisms in tuberculosis in our population.
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Context: Ifosfamide (IFA) is an effective antineoplastic for solid tumours in children, although it is associated with high levels of systemic toxicity and causes death in some cases. Objective: The aim of this study was to determine whether the presence of certain allelic variants of genes CYP2B6, CYP2C9, CYP3A4 and CYP3A5 increases the risk of toxicity in children with solid tumours treated with ifosfamide.Materials and methods: A total of 131 DNA samples were genotyped by real-time polymerase chain reaction (RT-PCR) using TaqMan probes. Toxicity was assessed using WHO criteria, and survival analysis was performed using Kaplan-Meier curves.Results: The rs3745274 allelic variant in CYP2B6 was associated with haematological toxicity, affecting neutrophils; CYP3A4 variant rs2740574 was also associated with toxicity, affecting both leukocytes and neutrophils. Additionally, the CYP3A5 gene variant rs776746 was found to affect haemoglobin.Conclusions: Our results show that allelic variants rs3745274 (CYP2B6), rs2740574 (CYP34) and rs776746 (CYP3A5) increase the risk for high haematological toxicity.Clinical trial registration: 068/2013.