Association study of genetic polymorphisms in proteins involved in oseltamivir transport, metabolism, and interactions with adverse reactions in Mexican patients with acute respiratory diseases.

Oseltamivir, a pro-drug, is the best option for treatment and chemoprophylaxis for influenza outbreaks. However, many patients treated with oseltamivir developed adverse reactions, including hypersensitivity, gastritis, and neurological symptoms. The aim of this study was to determine the adverse drug reactions (ADRs) in Mexican patients treated with oseltamivir and whether these ADRs are associated with SNPs of the genes involved in the metabolism, transport, and interactions of oseltamivir. This study recruited 310 Mexican patients with acute respiratory diseases and treated them with oseltamivir (75 mg/day for 5 days) because they were suspected to have influenza A/H1N1 virus infection. Clinical data were obtained from medical records and interviews. Genotyping was performed using real-time polymerase chain reaction and TaqMan probes. The association was assessed under genetic models with contingency tables and logistic regression analysis. Out of 310 patients, only 38 (12.25%) presented ADRs to oseltamivir: hypersensitivity (1.9%), gastritis (10%), and depression and anxiety (0.9%). The polymorphism ABCB1-rs1045642 was associated with adverse drug reactions under the recessive model (P = 0.017); allele C was associated with no adverse drug reactions, while allele T was associated with adverse drug reactions. The polymorphisms SLC15A1-rs2297322, ABCB1-rs2032582, and CES1-rs2307243 were not consistent with Hardy-Weinberg equilibrium, and no other associations were found for the remaining polymorphisms. In conclusion, the polymorphism rs1045642 in the transporter encoded by the ABCB1 gene is a potential predictive biomarker of ADRs in oseltamivir treatment.

Association between vitamin D receptor gene polymorphisms and pulmonary tuberculosis in a Mexican population.

BACKGROUND AND AIMS: The impact of host genetic variation in susceptibility of tuberculosis is well documented. The vitamin D receptor gene (VDR) is a transacting transcription factor which mediates innate immune response by enhancing the expression of several antimicrobial peptides, including cathelicidin. An association between VDR polymorphisms with tuberculosis (TB) has been investigated in different ethnic groups; however there are contradictions and inconsistencies in the results. The aim of this study was to evaluate the association between polymorphisms of functional VDR with the susceptibility to pulmonary tuberculosis in a Mexican population. METHODS: A case-control study was performed in, 257 patients with pulmonary tuberculosis and 457 healthy controls recruited from: family medicine clinics of the Mexican Social Security Institute. The VDR gene polymorphisms Fok I (rs 2228570), BsmI (rs1544410), ApaI (rs7975232) and TaqI (rs731236) were genotyped by TaqMan assays. Statistical analysis was performed using: Epi Info V-7 and SNP Stats software. RESULTS: No statistically significant associations were observed in genotype and haplotype distribution between BsmI, ApaI and TaqI polymorphisms and disease susceptibility. The CC genotype for the VDR gene FokI was significantly more frequent in patients than in controls (29.6% versus 17.5%, OR=1.97; 95% CI=1.37-2.8, PC=0.0004). Moreover, TT genotype was decreased in patients as compared to the control group (24.1% versus 34.8%, OR=0.59; 95% CI=0.42-0.84, PC=0.004). CONCLUSION: To our best knowledge, this is the first case-control study that finds an association between CC genotype of FokI SNP in the VDR gene with pulmonary tuberculosis in Mexican patients. However more validation studies should be performed to prove our conclusions.

In vitro transcribed RNA molecules for the diagnosis of pandemic 2009 influenza A(H1N1) virus by real-time RT-PCR.

The 2009 influenza A(H1N1) outbreak allowed the implementation of new epidemiologic surveillance tools in several countries around the world. A new molecular protocol with appropriate sensitivity and specificity using real-time RT-PCR was developed by the Centers for Disease Control and Prevention (CDC) to identify the pandemic 2009 influenza A (H1N1) virus in human specimens. In the CDC protocol, positive controls are available only upon request and they are taken from cell cultures infected with 2009 influenza A(H1N1) virus, representing a handling risk for laboratory technicians. The poor availability of positive control materials in diagnostic laboratories may limit the public health response. The aim of the work presented in this paper was to develop positive controls for the diagnostic testing of influenza A(H1N1) virus that could be used in the CDC real-time RT-PCR protocol. A series of plasmid constructs bearing partial sequences of the viral genes were created and each construct was used as a template for in vitro transcription. RNA molecules were obtained successfully at high yield, i.e., 2×10(7) assays per microliter. Thus, the inclusion of these molecules in the influenza panel as positive controls is proposed. The in vitro transcribed RNA could also be used as quality standards in the design of international proficiency studies.