PurposeWarfarin is an oral anticoagulant associated with adverse reaction to drugs due to wide inter- and intra-individual dosage variability. Warfarin dosage has been related to non-genetic and genetic factors. CYP2C9 and VKORC1 gene polymorphisms affect warfarin metabolism and dosage. Due to the central role of populations’ ethnical and genetic origin on warfarin dosage variability, novel algorithms for Latin American subgroups are necessary to establish safe anticoagulation therapy.Patients and methodsWe genotyped CYP2C9*2 (c.430C > T), CYP2C9*3 (c.1075A > C), CYP4F2 (c.1297G > A), and VKORC1 (−1639 G > A) polymorphisms in 152 Colombian patients who received warfarin. We evaluated the impact on the variability of patients’ warfarin dose requirements. Multiple linear regression analysis, using genetic and non-genetic variables, was used for creating an algorithm for optimal warfarin maintenance dose.ResultsMedian weekly prescribed warfarin dosage was significantly lower in patients having the VKORC1-1639 AA genotype and poor CYP2C9*2/*2,*2/*3 metabolizers than their wild-type counterparts. We found a 2.3-fold increase in mean dose for normal sensitivity patients (wild-type VKORC1/CYP2C9 genotypes) compared to the other groups (moderate and high sensitivity); 31.5% of the patients in our study group had warfarin sensitivity-related genotypes. The estimated regression equation accounted for 44.4% of overall variability in regard to warfarin maintenance dose. The algorithm was validated, giving 45.9% correlation (R2=0.459).ConclusionOur results describe and validate the first algorithm for predicting warfarin maintenance in a Colombian mestizo population and have contributed toward the understanding of pharmacogenetics in a Latin American population subgroup.

Aims: The 2009 H1N1 pandemic illustrated the higher morbidity and mortality from viral infections in peripartum women. We describe clinical features of women who recently died of H1N1 in Colombia. Methods: This is a case series study that was gathered through a retrospective record review of all maternal H1N1 deaths in the country. The national mortality database of confirmed mortality from H1N1 in pregnancy and up to 42 days after delivery was reviewed during the H1N1 season in 2009. Women with H1N1 infections were confirmed by the laboratory of virology. Demographic, clinical, and laboratory data were reviewed. Statistical analyses were performed and median values of non-parametric data were reported with inter-quartile range (IQR). Results: A total of 23 H1N1 maternal deaths were identified. Eighty-three percent occurred in the third trimester. None of the mothers who died had received influenza vaccination. The median time from symptom onset to the initiation of antiviral treatment was 8.8 days (IQR 5.8-9.8). Five fatalities did not receive any anti-viral therapy. Median PaO 2 /FiO 2 on day 1 was 80 (IQR, 60-98.5). All patients required inotropic support and mechanical ventilation with barotrauma-related complications of mechanical ventilation occurring in 35% of patients. Conclusion: In Colombia, none of the women suffering H1N1-related maternal deaths had received vaccination against the disease and most had delayed or had no antiviral therapy. Given the lack of evidence-based clinical predictors to identify women who are prone to die from H1N1 in pregnancy, following international guidelines for vaccination and initiation of antiviral therapy in suspected cases would likely improve outcomes in developing countries.

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There is a controversial relationship between HLA-A2 and Alzheimer's disease (AD). It has been suggested a modifier effect on the risk that depends on genetic loadings. Thus, the aims of this study were to evaluate this relationship and to reveal genes associated with both concepts the HLA-A gene and AD. Consequently, we did first a classical systematic review and a meta-analysis of case-control studies. Next, by means of an in silico approach, we used experimental knowledge of protein-protein interactions to evaluate the top ranked genes shared by both concepts, previously found through text mining. The meta-analysis did not show a significant pooled OR (1.11, 95% CI: 0.98 to 1.24 in Caucasians), in spite of the fact that four of the included studies had a significant OR > 1 and none of them a significant OR < 1. In contrast, the in silico approach retrieved nonrandomly shared genes by both concepts (P = 0.02), which additionally encode truly interacting proteins. The network of proteins encoded by APP, ICAM-1, ITGB2, ITGAL, SELP, SELL, IL2, IL1B, CD4, and CD8A linked immune to neurodegenerative processes and highlighted the potential roles in AD pathogenesis of endothelial regulation, infectious diseases, specific antigen presentation, and HLA-A2 in maintaining synapses.