An updated examination of the perception of barriers for pharmacogenomics implementation and the usefulness of drug/gene pairs in Latin America and the Caribbean.

Pharmacogenomics (PGx) is considered an emergent field in developing countries. Research on PGx in the Latin American and the Caribbean (LAC) region remains scarce, with limited information in some populations. Thus, extrapolations are complicated, especially in mixed populations. In this paper, we reviewed and analyzed pharmacogenomic knowledge among the LAC scientific and clinical community and examined barriers to clinical application. We performed a search for publications and clinical trials in the field worldwide and evaluated the contribution of LAC. Next, we conducted a regional structured survey that evaluated a list of 14 potential barriers to the clinical implementation of biomarkers based on their importance. In addition, a paired list of 54 genes/drugs was analyzed to determine an association between biomarkers and response to genomic medicine. This survey was compared to a previous survey performed in 2014 to assess progress in the region. The search results indicated that Latin American and Caribbean countries have contributed 3.44% of the total publications and 2.45% of the PGx-related clinical trials worldwide thus far. A total of 106 professionals from 17 countries answered the survey. Six major groups of barriers were identified. Despite the region's continuous efforts in the last decade, the primary barrier to PGx implementation in LAC remains the same, the "need for guidelines, processes, and protocols for the clinical application of pharmacogenetics/pharmacogenomics". Cost-effectiveness issues are considered critical factors in the region. Items related to the reluctance of clinicians are currently less relevant. Based on the survey results, the highest ranked (96%-99%) gene/drug pairs perceived as important were CYP2D6/tamoxifen, CYP3A5/tacrolimus, CYP2D6/opioids, DPYD/fluoropyrimidines, TMPT/thiopurines, CYP2D6/tricyclic antidepressants, CYP2C19/tricyclic antidepressants, NUDT15/thiopurines, CYP2B6/efavirenz, and CYP2C19/clopidogrel. In conclusion, although the global contribution of LAC countries remains low in the PGx field, a relevant improvement has been observed in the region. The perception of the usefulness of PGx tests in biomedical community has drastically changed, raising awareness among physicians, which suggests a promising future in the clinical applications of PGx in LAC.

Efecto del fraccionamiento de la dieta y cantidad de hidratos de carbono en el control metabólico en pacientes con diabetes mellitus tipo 2, sin terapia con insulina / Effect of meal frequency and carbohydrate intake on the metabolic control of patients with type 2 diabetes mellitus

Background: Increasing meal frequency is commonly used in the clinical practice as part of the nutritional treatment of patients with type 2 Diabetes Mellitus (DM2), although its effect on metabolic control parameters is controversial. Aim: To evaluate the association of energy intake, meal frequency, and amount of carbohydrates with fasting plasma glucose and glycosylated hemoglobin in a group of patients with DM2 without insulin therapy. Material and Methods: Dietary intake was evaluated in 60 subjects with DM2 through three-day food records. The meal frequency was estimated establishing the main meal times considering snacks. Results: Meal frequency was 4.7 ± 1.1 times per day. There was a positive association between glycosylated and fasting blood glucose levels (p <0.01). Meal frequency was associated with energy intake (p <0.01). When meal frequency, available carbohydrates and energy intake, body mass index and fasting plasma glucose were analyzed in a multiple linear regression model, fasting blood glucose was the variable that best predicted changes in glycosylated hemoglobin (45.5%). Meal frequency had no association with glycosylated hemoglobin. Conclusions: Meal frequency showed no association with metabolic control parameters in DM2 patients.

Analysis of Mycobacterium tuberculosis Genotypic Lineage Distribution in Chile and Neighboring Countries.

Tuberculosis (TB), caused by the pathogen Mycobacterium tuberculosis (MTB), remains a disease of high importance to global public health. Studies into the population structure of MTB have become vital to monitoring possible outbreaks and also to develop strategies regarding disease control. Although Chile has a low incidence of MTB, the current rates of migration have the potential to change this scenario. We collected and analyzed a total of 458 M. tuberculosis isolates (1 isolate per patient) originating from all 15 regions of Chile. The isolates were genotyped using the spoligotyping method and the data obtained were analyzed and compared with the SITVIT2 database. A total of 169 different patterns were identified, of which, 119 patterns (408 strains) corresponded to Spoligotype International Types (SITs) and 50 patterns corresponded to orphan strains. The most abundantly represented SITs/lineages were: SIT53/T1 (11.57%), SIT33/LAM3 (9.6%), SIT42/LAM9 (9.39%), SIT50/H3 (5.9%), SIT37/T3 (5%); analysis of the spoligotyping minimum spanning tree as well as spoligoforest were suggestive of a recent expansion of SIT42, SIT50 and SIT37; all of which potentially evolved from SIT53. The most abundantly represented lineages were LAM (40.6%), T (34.1%) and Haarlem (13.5%). LAM was more prevalent in the Santiago (43.6%) and Concepción (44.1%) isolates, rather than the Iquique (29.4%) strains. The proportion of X lineage was appreciably higher in Iquique and Concepción (11.7% in both) as compared to Santiago (1.6%). Global analysis of MTB lineage distribution in Chile versus neighboring countries showed that evolutionary recent lineages (LAM, T and Haarlem) accounted together for 88.2% of isolates in Chile, a pattern which mirrored MTB lineage distribution in neighboring countries (n = 7378 isolates recorded in SITVIT2 database for Peru, Brazil, Paraguay, and Argentina; and published studies), highlighting epidemiological advantage of Euro-American lineages in this region. Finally, we also observed exclusive emergence of patterns SIT4014/X1 and SIT4015 (unknown lineage signature) that have hitherto been found exclusively in Chile, indicating that conditions specific to Chile, along with the unique genetic makeup of the Chilean population, might have allowed for a possible co-evolution leading to the success of these emerging genotypes.

[Effect of meal frequency and carbohydrate intake on the metabolic control of patients with type 2 diabetes mellitus]. / Efecto del fraccionamiento de la dieta y cantidad de hidratos de carbono en el control metabólico en pacientes con diabetes mellitus tipo 2, sin terapia con insulina.

BACKGROUND: Increasing meal frequency is commonly used in the clinical practice as part of the nutritional treatment of patients with type 2 Diabetes Mellitus (DM2), although its effect on metabolic control parameters is controversial. AIM: To evaluate the association of energy intake, meal frequency, and amount of carbohydrates with fasting plasma glucose and glycosylated hemoglobin in a group of patients with DM2 without insulin therapy. MATERIAL AND METHODS: Dietary intake was evaluated in 60 subjects with DM2 through three-day food records. The meal frequency was estimated establishing the main meal times considering snacks. RESULTS: Meal frequency was 4.7 ± 1.1 times per day. There was a positive association between glycosylated and fasting blood glucose levels (p <0.01). Meal frequency was associated with energy intake (p <0.01). When meal frequency, available carbohydrates and energy intake, body mass index and fasting plasma glucose were analyzed in a multiple linear regression model, fasting blood glucose was the variable that best predicted changes in glycosylated hemoglobin (45.5%). Meal frequency had no association with glycosylated hemoglobin. CONCLUSIONS: Meal frequency showed no association with metabolic control parameters in DM2 patients.

[Detection of genes associated with drug resistance in Mycobacterium tuberculosis strains isolated in Chile]. / Detección de mutaciones asociadas a cepas multidrogo resistente de Mycobacterium tuberculosis en Chile.

BACKGROUND: The incidence of acquired resistance to antituberculous drugs of Mycobacterium tuberculosis in Chile is approximately 23%. AIM: To analyze the mutations associated with drug resistance in drug resistant strains of Mycobacterium tuberculosis. MATERIAL AND METHODS: In 28 drug resistant Mycobacterium tuberculosis strains isolated in Chile, genes leading to drug resistance were studied. DNA was amplified by polymerase chain reaction (PCR) and sequencing was carried out using the ABI PRISM big dye terminator cycle sequencing ready reaction kit. RESULTS: In rifampicin-resistant strains, the mutations in rpoß gene were in the codons S531W/L (56%), D516Y (16%) and D516V (16%). The predominant mutation in katG gene was in the codon S315L (73%) in isoniazid-resistant strains. The mutation S95T was found in the 71% of ciprofloxacin resistant strains. Only one ethambutol resistant strain had the M306I mutation. Three unreported mutations in katG were identified. CONCLUSIONS: Drug resistance associated mutations of Mycobacterium tuberculosis isolated in Chile were similar to those reported abroad.

Detección de mutaciones asociadas a cepas multidrogo resistente de Mycobacterium tuberculosis en Chile / Detection of genes associated with drug resistance in Mycobacterium tuberculosis strains isolated in Chile

Background: The incidence of acquired resistance to antituberculous drugs of Mycobacterium tuberculosis in Chile is approximately 23 percent. Aim: To analyze the mutations associated with drug resistance in drug resistant strains of Mycobacterium tuberculosis. Material and Methods: In 28 drug resistant Mycobacterium tuberculosis strains isolated in Chile, genes leading to drug resistance were studied. DNA was amplifed by polymerase chain reaction (PCR) and sequencing was carried out using the ABI PRISM big dye terminator cycle sequencing ready reaction kit. Results: In rifampicin-resistant strains, the mutations in rpoβ gene were in the codons S531W/L (56 percent), D516Y (16 percent) and D516V (16 percent). The predominant mutation in katG gene was in the codon S315L (73 percent) in isoniazid-resistant strains. The mutation S95T was found in the 71 percent of ciprofoxacin resistant strains. Only one ethambutol resistant strain had the M306I mutation. Three unreported mutations in katG were identifed. Conclusions: Drug resistance associated mutations of Mycobacterium tuberculosis isolated in Chile were similar to those reported abroad.