Comprehensive Screening of Genetic Variants in the Coding Region of F8 in Severe Hemophilia A Reveals a Relationship with Disease Severity in a Colombian Cohort.

Hemophilia A is an X-linked disorder characterized by quantitative deficiency of coagulation factor VIII (FVIII) caused by pathogenic variants in the factor 8 (F8) gene. Our study's primary objective was to identify genetic variants within the exonic region of F8 in 50 Colombian male participants with severe hemophilia A (HA). Whole-exome sequencing and bioinformatics analyses were performed, and bivariate analysis was used to evaluate the relationship between identified variants, disease severity, and inhibitor risk formation. Out of the 50 participants, 21 were found to have 17 different pathogenic F8 variants (var). It was found that 70% (var = 12) of them were premature truncation variants (nonsense, frameshift), 17.6% (var = 3) were missense mutations, and 11.7% (var = 2) were splice-site variants. Interestingly, 35% (var = 6) of the identified variants have not been previously reported in the literature. All patients with a history of positive inhibitors (n = 4) were found to have high-impact genetic variants (nonsense and frameshift). When investigating the relationship between variant location (heavy versus light chain) and specific inhibitor risk, 75% (n = 3) of the inhibitor participants were found to have variants located in the F8 light chain (p = 0.075), suggesting that conserved domains are associated with higher inhibitor risk. In summary, we identified genetic variants within the F8 that can possibly influence inhibitor development in Colombian patients with severe HA. Our results provide a basis for future studies and the development of further personalized treatment strategies in this population.

Calidad de vida relacionada con la salud en tuberculosis: Revisión sistemática y metanálisis / Health related Quality of life in tuberculosis: a systematic review and metanalyses

Objetivo: Realizar un metanalisis sobre el efecto de la tuberculosis sobre las dimensiones del SF-36. Material y métodos: Revisión sistemática y metanálisis según la guía PRISMA, garantizando reproducibilidad y calidad metodológica con la guía STROBE. Se realizó metanálisis aplicando Dersimonian y Laird's, Begg, Egger y análisis de sensibilidad, en el software EPIDAT 3.1. Resultados: Se incluyeron 35 estudios con 12.159 personas y ocho constructos diferentes de calidad de vida. En el SF-36 los enfermos presentaron peor calidad de vida frente a individuos sanos, con diferencias de 51,5 puntos en función física y salud mental, 47,1 en desempeño social, 41,1 en salud general, 33,7 en energía, 27,4 en desempeño emocional, 24,9 en desempeño físico y 5,7 en el dolor corporal. Conclusión: Existe una alta disponbilidad de constructos de calidad de vida en tuberculosis, la enfermedad impacta negativamente la función física, salud mental y desempeño social, lo que evidencia la necesidad de un enfoque de atención multidimensional e interdisciplinar.

Objective: To perform a metanalysis on the effect of the tuberculosis on the dimensions of the SF-36. Methods: Systematic review and meta-analysis, following the PRISMA guide. The reproducibility was guaranteed and methodological quality was evaluated with STROBE guide. Random effects meta-analysis was performed using the Dersimonian and Laird's tests, Begg, Egger and sensitivity analyzes in EPIDAT 3.1. Results: We included 35 studies with 12 159 people and eight different constructs of quality of life. In the SF-36, people with tuberculosis had a lower score than healthy controls, with differences of 51.5 points in physical function and mental health, 47.1 in social performance, 41.1 in general health, 33.7 in energy, 27.4 in emotional performance, 24.9 in physical performance and 5.7 in body pain. Conclusion: There is a high availability of quality of life constructs for people with tuberculosis, the disease generates negative impacts on physical function, mental health and social performance, which evidences the need for a multidimensional and interdisciplinary approach for this population.

Palenque de San Basilio in Colombia: genetic data support an oral history of a paternal ancestry in Congo.

The Palenque, a black community in rural Colombia, have an oral history of fugitive African slaves founding a free village near Cartagena in the seventeenth century. Recently, linguists have identified some 200 words in regular use that originate in a Kikongo language, with Yombe, mainly spoken in the Congo region, being the most likely source. The non-recombining portion of the Y chromosome (NRY) and mitochondrial DNA were analysed to establish whether there was greater similarity between present-day members of the Palenque and Yombe than between the Palenque and 42 other African groups (for all individuals,n= 2799) from which forced slaves might have been taken. NRY data are consistent with the linguistic evidence that Yombe is the most likely group from which the original male settlers of Palenque came. Mitochondrial DNA data suggested substantial maternal sub-Saharan African ancestry and a strong founder effect but did not associate Palenque with any particular African group. In addition, based on cultural data including inhabitants' claims of linguistic differences, it has been hypothesized that the two districts of the village (Abajo and Arriba) have different origins, with Arriba founded by men originating in Congo and Abajo by those born in Colombia. Although significant genetic structuring distinguished the two from each other, no supporting evidence for this hypothesis was found.

Amerind ancestry, socioeconomic status and the genetics of type 2 diabetes in a Colombian population.

The "thrifty genotype" hypothesis proposes that the high prevalence of type 2 diabetes (T2D) in Native Americans and admixed Latin Americans has a genetic basis and reflects an evolutionary adaptation to a past low calorie/high exercise lifestyle. However, identification of the gene variants underpinning this hypothesis remains elusive. Here we assessed the role of Native American ancestry, socioeconomic status (SES) and 21 candidate gene loci in susceptibility to T2D in a sample of 876 T2D cases and 399 controls from Antioquia (Colombia). Although mean Native American ancestry is significantly higher in T2D cases than in controls (32% v 29%), this difference is confounded by the correlation of ancestry with SES, which is a stronger predictor of disease status. Nominally significant association (P<0.05) was observed for markers in: TCF7L2, RBMS1, CDKAL1, ZNF239, KCNQ1 and TCF1 and a significant bias (P<0.05) towards OR>1 was observed for markers selected from previous T2D genome-wide association studies, consistent with a role for Old World variants in susceptibility to T2D in Latin Americans. No association was found to the only known Native American-specific gene variant previously associated with T2D in a Mexican sample (rs9282541 in ABCA1). An admixture mapping scan with 1,536 ancestry informative markers (AIMs) did not identify genome regions with significant deviation of ancestry in Antioquia. Exclusion analysis indicates that this scan rules out ~95% of the genome as harboring loci with ancestry risk ratios >1.22 (at P < 0.05).

Exposure of Red Tilapia (Oreochromis spp.) eggs to 17 α-Methyltestosterone and the sex ratio of the fish offspring / Inmersión de ovas de tilapia roja (Oreochromis spp.) en diferentes estadíos de fertilización en una solución de 17 α- metiltestosterona y la proporción fenotípica del sexo / Efeito da imersão de ovas de tilápia vermelha (Oreochromis spp.) em diferentes fases de fertilização numa solução de 17α- metiltestosterona sobre a proporção fenotípica do sexo

This study evaluated the proportions of sex reversals which occurred after red tilapia (Oreochromis spp.) eggs were immersed into various solutions of 17 α-Methyltestosterone (0, 800 and 1200 ug/L of water). Two fertilization stages of the eggs, i.e., reflecting clear or dark colors, were included in this study. Besides sex proportions, other parameters studied included hatching, fry and fingerling survival, final weight and length. There were no significant differences between the sex proportions obtained relative to hormone concentration or egg color (49.59% males from dark eggs and 46.36% males from light eggsversus the control, which had 55.24% males). In contrast, the percentage of hatching was significantly higher in dark eggs (60.27% ± 11.52). Survival of fry was higher when born from dark eggs compared with clear eggs (51.74% ± 27.01 versus 28.97% ± 1.52, respectively). Fingerling survival was not related to the color of the eggs (59.28% ± 23.73 versus 65.58% ± 9.01 for initially dark and clear eggs, respectively). However, surviving males were longer and heavier (6.75 cm ± 1.29 and 5.45 g ± 3.09) than females. This data suggest a possible interaction between hatching, survival, and egg color.

Este trabajo tuvo como objetivo evaluar la reversión sexual por inmersión de ovas de tilapia roja (Oreochromis spp.) clasificadas por estadíos de fertilización (color de ovas claras y oscuras) a diferentes hormonales 0, 800 y 1200 μg de 17 α- Metil Testosterona (17αMT/L) por litro de agua. El trabajo fue realizado en la estación piscícola de la Universidad de Antioquia, midiendo como variables: proporción sexual, porcentaje de eclosión, sobrevivencia en larva y alevinaje, peso final, longitud total. Para porcentaje de reversión sexual no se encontró diferencia significativa (p>0.05) con respecto a las concentraciones hormonales y al color de ovas, cuyos valores promedio fueron 49.59% de machos para ovas oscuras y 46.36% de machos para ovas claras, respecto al tratamiento testigo que tuvo 55.24% de machos. Para los demás parámetros, tales como porcentaje de eclosión, se encontró diferencia altamente significativa (p<0.01) con respecto al color de las ovas siendo mayor la eclosión en ovas de color oscuro con un valor de 60.27 ± 11.52%. Para sobrevivencia en larva se encontró diferencia significativa (p<0.05) hallándose 51.74 ± 27.01% para las larvas provenientes de ovas oscuras y 28.97 ± 1.52% para las provenientes de ovas claras. Para sobrevivencia en la etapa de alevinaje, no hubo diferencia significativa (p>0.05) con respecto al color de las ovas, encontrándose 59.2 ± 23.73% para los animales provenientes de ovas oscuras y de 65.58 ± 9.01% para los animales provenientes de ovas claras. En las variables peso y longitud se observó diferencia altamente significativa (p<0.001) con respecto al sexo siendo de mayor tamaño y peso los machos con una media de 6.75 ± 1.29 cm y 5.45 ± 3.09 g, respectivamente.

Este estudo teve como objetivo avaliar a reversão sexual por imersão em ovas de tilápia vermelha (Oreochromis spp.), classificadas por fases da fecundação (ovas de cores claras e escuras), com diferentes concentrações hormonais, 0, 800 e 1200 μg17α MT / L de água. Este trabalho foi realizado na Estação Piscícola da Universidade de Antioquia, medindo variáveis, tais como: percentagem de Eclosão, percentagem de Sobrevivência das larvas e alevinagem, Peso fim, Comprimento total, e proporção sexual. Para a variável Eclosão, foi encontrada uma diferença altamente significativa (p<0.01), sendo maior a quantidade de ovas escuras, com uma média de 60.27% e um desvio padrão de ± 11.52%. Na sobrevivencia das larvas não foi encontrada diferença significativa (p<0.05) com respeito a cor das ovas, havendo uma média de 51.74% e um desvio padrão de ± 27.01% para as larvas das ovas escuras; uma média de 28.97% e com desvio padrão de ± 1.52% para as larvas das ovas claras. Durante a etapa da alevinagem não houve diferença significativa (p>0.05), encontrado uma média de 59.28% e um desvio padrão de ± 23.73% para os animais provenientes de ovas escuras; uma média de 65.58% e um desvio padrão de ± 9.01% para animais provenientes de ovas claras. Nas variáveis Peso e Comprimento, foi observada diferença altamente significativa (p <0.001); sendo os machos, de maior tamanho e peso, com uma média de 6.75 centímetros e um desvio padrão de ± 1.29 cm para a variável comprimento. Para a variável peso, ocorreu uma média de 5.45 gr e um desvio de ± 3.09 g. Para a Reversão, não foi encontrada diferença significativa (p>0.05), no que diz respeito ao concentrações hormonais e a cor das ovas.

[Association between polymorphism in uncoupling proteins and type 2 diabetes in a northwestern Colombian population]. / Asociación de variantes en genes de las proteínas desacoplantes con diabetes mellitus tipo 2 en una población del nordeste colombiano.

INTRODUCTION: The uncoupling proteins belong to the family of anion transporting proteins which uncouple the ATP production from the mitochondrial respiration, cause proton leakage through the inner mitochondrial membrane, and release energy as heat. Although uncoupling protein function has not been well established, specific polymorphisms in these proteins have been associated with type 2 diabetes mellitus, obesity and insulin resistance. OBJECTIVE: The association was assessed between the polymorphisms in uncoupling protein genes 1, 2 and 3 genes and type 2 diabetes mellitus. MATERIALS AND METHODS: In a northwestern Colombian population, 545 diabetes cases and 449 controls were investigated for presence of 14 polymorphisms in uncoupling protein genes (3826A/G, ID 45, 2723T/A, 1957G/A, 866G/A, and 55C/T) by PCR and PCR-RFLP. Single associations were evaluated by chi-square test, and bayesian logistic regression analysis was done including as covariates the individual admixture estimates obtained by 54 informative markers for European, African and Amerind ancestry. RESULTS: Association between type 2 diabetes mellitus and the polymorphisms 3826A (OR=0.78; 95% CI = 0.63-0.97; p = 0.02) and 55 C (OR = 1.41; 95% CI = 1.04-1.92; p = 0.03) and the haplotype D45, 866G, 1957G, 2723T, and 55C (OR = 1.26; 95% CI = 1.02-1.56; p = 0.03) were found. These associations remained after adjustment using individual genetic admixture estimates. CONCLUSION: Some alleles of uncoupling protein genes 1, 2 and 3, and their haplotypes confer risk to type 2 diabetes in a northwestern Colombian population.

Asociación de variantes en genes de las proteínas desacoplantes con diabetes mellitus tipo 2 en una población del nordeste colombiano / Association between polymorphism in uncoupling proteins and type 2 diabetes in a northwestern Colombian population

Introducción. Las proteínas desacoplantes pertenecen a la familia de proteínas transportadoras de aniones que desacoplan la producción de ATP de la respiración mitocondrial, causando pérdida de protones a través de la membrana mitocondrial interna y disipando la energía en forma de calor. Aunque su función no ha sido bien establecida, algunos polimorfismos en estas proteínas se han asociado con diabetes mellitus tipo 2, obesidad y resistencia a la insulina. Objetivo. Evaluar la asociación entre las variantes -3826A/G, ID 45, -2723T/A, -1957G/A, -866G/A, -55C/T de los genes de las proteínas desacoplantes 1, 2 y 3 con diabetes mellitus tipo 2 en una población del nordeste colombiano. Materiales y métodos. Se tipificaron 545 casos y 449 controles para 14 variantes de los genes de las proteínas desacoplantes por medio de PCR y PCR-RFLP. Se hicieron pruebas de asociación simples con ji al cuadrado y se corrigieron en un análisis de regresión logística bayesiana, incluyendo los estimados de mezcla individual obtenidos mediante 54 marcadores informativos de ascendencia europea, africana y amerindia. Resultados. Las variantes -3826A (OR=0,78; IC95% 0,63-0,97; p=0,02), -55C (OR=1,41; IC95% 1,04-1,92; p=0,03) de las proteínas desacoplantes 1 y 3, respectivamente, y el haplotipo D45, -866G, -1957G, -2723T, -55C (OR=1,26; IC95% 1,02-1,56; p=0,03) se asociaron con diabetes tipo 2. Estas asociaciones se conservaron después de ajustar por la mezcla genética individual. Conclusión. Algunas variantes de las proteínas desacoplantes 1, 2 y 3, y sus haplotipos, confieren riesgo para diabetes mellitus tipo 2 en una población del nordeste colombiano.

Introduction. The uncoupling proteins belong to the family of anion transporting proteins which uncouple the ATP production from the mitochondrial respiration, cause proton leakage through the inner mitochondrial membrane, and release energy as heat. Although uncoupling protein function has not been well established, specific polymorphisms in these proteins have been associated with type 2 diabetes mellitus, obesity and insulin resistance. Objective. The association was assessed between the polymorphisms in uncoupling protein genes 1, 2 and 3 genes and type 2 diabetes mellitus. Materials and methods. In a northwestern Colombian population, 545 diabetes cases and 449 controls were investigated for presence of 14 polymorphisms in uncoupling protein genes (3826A/G, ID 45, 2723T/A, 1957G/A, 866G/A, and 55C/T) by PCR and PCR-RFLP. Single associations were evaluated by chi-square test, and bayesian logistic regression analysis was done including as covariates the individual admixture estimates obtained by 54 informative markers for European, African and Amerind ancestry. Results. Association between type 2 diabetes mellitus and the polymorphisms 3826A (OR=0.78; 95%CI=0.63-0.97; p=0.02) and 55C (OR=1.41; 95%CI=1.04-1.92; p=0.03) and the haplotype D45, 866G, 1957G, 2723T, and 55C (OR=1.26; 95%CI=1.02-1.56; p=0.03) were found. These associations remained after adjustment using individual genetic admixture estimates. Conclusion. Some alleles of uncoupling protein genes 1, 2 and 3, and their haplotypes confer risk to type 2 diabetes in a northwestern Colombian population.