The distribution of allelic and genotypic frequencies of N-Acetyltransferase-2 variants in an Argentine population.

INTRODUCTION: Arylamine N-acetyltransferase-2 (NAT-2) is a key human enzyme in drug detoxification and elimination. Mutations in NAT-2 affect the activity of anti-tuberculosis drugs and result in three different phenotypes: rapid (RA), intermediate (IA) and slow acetylators (SA). METHODOLOGY: The allelic, genotypic and phenotypic frequencies of NAT-2 were studied in 185 patients from Buenos Aires by restriction fragment length polymorphism. RESULTS: The following allele frequencies were obtained: *4 = 29.9%, *5 = 37.0, *6 = 25.6%, *7 = 8% and *14 = 1.3%. With regard to the phenotype, we observed that 53.6% of the population was SA, 35.7% was IA and 10.7% was RA. CONCLUSION: A high prevalence of SA might have an impact on anti-TB drug-induced hepatotoxicity.

Biomarkers in sepsis at time zero: intensive care unit scores, plasma measurements and polymorphisms in Argentina.

INTRODUCTION: A patient's response to sepsis is influenced by their genetic background. Our objective was to use plasma markers, such as protein C (PC), D-dimer, Plasminogen Activator Inhibitor-1 (PAI-1) levels, and the PAI-1 rs1799889 4G/5G and  Tumor Necrosis Factor-α rs1800629 G/A  polymorphisms to improve classical intensive care unit (ICU) scores. METHODOLOGY: We studied 380 subjects, 166 with sepsis. We performed coagulation tests: plasma PAI-1 and PC levels were evaluated by chromogenic methods; and D-dimer was evaluated by immunoturbidimetric assay. Polymorphisms were performed using for polymerase chain reactions followed by digest with specific restriction enzyme. We acquired the APACHE and SOFA scores (time zero), sex, age, body mass index, associated co-morbidities, length of ICU stay (days), the severity of sepsis (sepsis, severe sepsis or septic shock), the HIV status and the ICU outcome (survival or death). RESULTS: We found significant differences between patients who died (n=80) and those who survived (n=86) in terms of the ICU length of stay (6 vs. 10 days), septic shock (64 versus 24%), age (51 versus 38 years old), HIV+ condition (34 versus 16%), SOFA (7 versus 4), APACHE (19 versus 13), D-dimer (4.32 versus 2.88 mg/ml), PC (46.0 versus 63.5 %) and PAI-1 (33.0 versus 16.5 UA/l). When we used a regression analysis with dichotomized variables, only the SOFA4, PAI-116, HIV status and the PAI-1 4G allele proved to be predictors of death at time zero. CONCLUSIONS: In the future, ICU scores may be further improved by adding certain genomic or plasma data.