Lamb-Shaffer syndrome: 20 Spanish patients and literature review expands the view of neurodevelopmental disorders caused by SOX5 haploinsufficiency.

Lamb-Shaffer Syndrome (LSS; OMIM #616803; ORPHA #313892; ORPHA #313884) is an infrequent genetic disorder that affects multiple aspects of human development especially those related to the development of the nervous system. LSS is caused by variants in the SOX5 gene. At the molecular level, SOX5 gene encodes for a transcription factor containing a High Mobility Group (HMG) DNA-Binding domain with relevant functions in brain development in different vertebrate species. Clinical features of Lamb-Shaffer syndrome may include intellectual disability, delayed speech and language development, attention deficits, hyperactivity, autism spectrum disorder, visual problems and seizures. Additionally, patients with the syndrome may present distinct facial dimorphism such as a wide mouth with full lips, small chin, broad nasal bridge, and deep-set eyes. Other physical features that have been reported in some patients include short stature, scoliosis, and joint hypermobility. Here, we report the clinical and molecular characterization of a Spanish LSS cohort of new 20 patients and review all the patients published so far which amount for 111 patients. The most frequent features included developmental delay, intellectual disability, visual problems, poor speech development and facial dysmorphic features. Strikingly, pain insensitivity and hypermetropia seems to be more frequent than previously reported, based on the frequency seen in the Spanish cohort. Eighty-three variants have been reported so far, single nucleotide variants (SNV) and copy number variants represent 47% and 53%, respectively, from the total of variants reported. Similarly to previous reports, the majority of the SNVs variants of the novel patients reported herein fall in the HMG domain of the protein. However, new variants, affecting other functional domains, were also detected. In conclusion, LLS is a rare genetic disorder mostly characterized by a wide range of developmental and neurological symptoms. Early diagnosis would allow to start of care programs, clinical follow up, prospective studies and appropriate genetic counseling, to promote clinical and social improvement to have profound lifelong benefits for patients and their families. Further research is needed to better understand the underlying mechanisms of the syndrome related to SOX5 haploinsufficiency.

Novel Loss-of-Function KCNA5 Variants in Pulmonary Arterial Hypertension.

Reduced expression and/or activity of Kv1.5 channels (encoded by KCNA5) is a common hallmark in human or experimental pulmonary arterial hypertension (PAH). Likewise, genetic variants in KCNA5 have been found in patients with PAH, but their functional consequences and potential impact on the disease are largely unknown. Herein, this study aimed to characterize the functional consequences of seven KCNA5 variants found in a cohort of patients with PAH. Potassium currents were recorded by patch-clamp technique in HEK293 cells transfected with wild-type or mutant Kv1.5 cDNA. Flow cytometry, Western blot, and confocal microscopy techniques were used for measuring protein expression and cell apoptosis in HEK293 and human pulmonary artery smooth muscle cells. KCNA5 variants (namely, Arg184Pro and Gly384Arg) found in patients with PAH resulted in a clear loss of potassium channel function as assessed by electrophysiological and molecular modeling analyses. The Arg184Pro variant also resulted in a pronounced reduction of Kv1.5 expression. Transfection with Arg184Pro or Gly384Arg variants decreased apoptosis of human pulmonary artery smooth muscle cells compared with the wild-type cells, demonstrating that KCNA5 dysfunction in both variants affects cell viability. Thus, in addition to affecting channel activity, both variants were associated with impaired apoptosis, a crucial process linked to the disease. The estimated prevalence of dysfunctional KCNA5 variants in the PAH population analyzed was around 1%. The data indicate that some KCNA5 variants found in patients with PAH have critical consequences for channel function, supporting the idea that KCNA5 pathogenic variants may be a causative or contributing factor for PAH.

A large, ten-generation family with autosomal dominant preaxial polydactyly/triphalangeal thumb: Historical, clinical, genealogical, and molecular studies.

We present a large, ten-generation family of 273 individuals with 84 people having preaxial polydactyly/triphalangeal thumb due to a pathogenic variant in the zone of polarizing activity regulatory sequence (ZRS) within the exon 5 of LMBR1. The causative change maps to position 396 of the ZRS, located at position c.423 + 4909C > T (chr7:156791480; hg38; LMBR1 ENST00000353442.10; rs606231153 NG_009240.2) in the intron 5 of LMBR1. The first affected individual with the disorder was traced back to mid-1700, when some settlers and workers established in Cervera de Buitrago, a small village about 82 km North to Madrid. Clinical and radiological studies of most of the affected members have been performed for 42 years (follow-up of the family by LFGA). Molecular studies have confirmed a pathogenic variant in the ZRS that segregates in this family. To the best of our knowledge, this is the largest family with preaxial polydactyly/triphalangeal thumb reported so far.

Pain and health-related quality of life in patients with hypophosphatasemia with and without ALPL gene mutations.

Background: Low serum alkaline phosphatase levels are the hallmark of hypophosphatasia, a disorder due to pathogenic variants of the ALPL gene. However, some patients do not carry ALPL variants and the cause of low alkaline phosphatase remains unknown. We aimed to determine health-related quality of life in adults with low alkaline phosphatase and explore the differences between patients with and without ALPL mutations. Methods: We studied 35 adult patients with persistently low alkaline phosphatase unrelated to secondary acquired causes who had ALPL sequenced, and 35 controls of similar age. Three questionnaires about body pain (Brief Pain Inventory, BPI), physical disability (Health Assessment Questionnaire Disability Index, HAQ-DI), and health-related quality of life (36-item Short-Form Health Survey, SF-36) were delivered by telephone interviews. Results: The mean BPI intensity and interference scores were higher in the patient group (p=0.04 and 0.004, respectively). All domains of the HAQ instrument tended to score better in the control group, with significant differences in the "reach" score (p=0.037) and the overall mean score (0.23 vs 0.09; p=0.029). Patients scored worse than controls in several SF-36 dimensions (Role physical, p=0.039; Bodily pain p=0.046; Role emotional, p=0.025). Patients with and without pathogenic variants scored similarly across all tests, without between-group significant differences. Conclusions: Patients with persistently low levels of alkaline phosphatase have significantly worse scores in body pain and other health-related quality of life dimensions, without differences between patients with and without pathogenic variants identified in ALPL gene. This is consistent with the latter ones carrying mutations in regulatory regions.

Clinical Spectrum and Tumour Risk Analysis in Patients with Beckwith-Wiedemann Syndrome Due to CDKN1C Pathogenic Variants.

Beckwith-Wiedemann syndrome spectrum (BWSp) is an overgrowth disorder caused by imprinting or genetic alterations at the 11p15.5 locus. Clinical features include overgrowth, macroglossia, neonatal hypoglycaemia, omphalocele, hemihyperplasia, cleft palate, and increased neoplasm incidence. The most common molecular defect observed is hypomethylation at the imprinting centre 2 (KCNQ1OT1:TSS DMR) in the maternal allele, which accounts for approximately 60% of cases, although CDKN1C pathogenic variants have been reported in 5-10% of patients, with a higher incidence in familial cases. In this study, we examined the clinical and molecular features of all cases of BWSp identified by the Spanish Overgrowth Registry Initiative with pathogenic or likely pathogenic CDKN1C variants, ascertained by Sanger sequencing or next-generation sequencing, with special focus on the neoplasm incidence, given that there is scarce knowledge of this feature in CDKN1C-associated BWSp. In total, we evaluated 21 cases of BWSp with CDKN1C variants; 19 were classified as classical BWS according to the BWSp scoring classification by Brioude et al. One of our patients developed a mediastinal ganglioneuroma. Our study adds evidence that tumour development in patients with BWSp and CDKN1C variants is infrequent, but it is extremely relevant to the patient's follow-up and supports the high heterogeneity of BWSp clinical features associated with CDKN1C variants.

Expanding the Evidence of a Semi-Dominant Inheritance in GDF2 Associated with Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) sometimes co-exists with hereditary hemorrhagic telangiectasia (HHT). Despite being clinically diagnosable according to Curaçao criteria, HHT can be difficult to diagnose due to its clinically heterogenicity and highly overlapping with PAH. Genetic analysis of the associated genes ACVRL1, ENG, SMAD4 and GDF2 can help to confirm or discard the presumptive diagnosis. As part of the clinical routine and to establish a genetic diagnosis, we have analyzed a cohort of patients with PAH and overlapping HHT features through a customized Next Generation Sequencing (NGS) panel of 21 genes, designed and validated in-house. We detected a homozygous missense variant in GDF2 in a pediatric patient diagnosed with PAH associated with HHT and a missense variant along with a heterozygous deletion in another idiopathic PAH patient (compound heterozygous inheritance). In order to establish variant segregation, we analyzed all available family members. In both cases, parents were carriers for the variants, but neither was affected. Our results expand the clinical spectrum and the inheritance pattern associated with GDF2 pathogenic variants suggesting incomplete penetrance and/or variability of expressivity with a semi-dominant pattern of inheritance.

Tenorio syndrome: Description of 14 novel cases and review of the clinical and molecular features.

Tenorio syndrome (TNORS) (OMIM #616260) is a relatively recent disorder with very few cases described so far. Clinical features included macrocephaly, intellectual disability, hypotonia, enlarged ventricles and autoimmune diseases. Molecular underlying mechanism demonstrated missense variants and a large deletion encompassing RNF125, a gene that encodes for an U3 ubiquitin ligase protein. Since the initial description of the disorder in six patients from four families, several new patients were diagnosed, adding more evidence to the clinical spectrum. In this article, we described 14 additional cases with deep phenotyping and make an overall review of all the cases with pathogenic variants in RNF125. Not all patients presented with overgrowth, but instead, most patients showed a common pattern of neurodevelopmental disease, macrocephaly and/or large forehead. Segregation analysis showed that, though the variant was inherited in some patients from an apparently asymptomatic parent, deep phenotyping suggested a mild form of the disease in some of them. The mechanism underlying the development of this disease is not well understood yet and the report of further cases will help to a better understanding and clinical characterization of the syndrome.

Novel Genetic and Molecular Pathways in Pulmonary Arterial Hypertension Associated with Connective Tissue Disease.

Pulmonary Arterial Hypertension (PAH) is a severe complication of Connective Tissue Disease (CTD), with remarkable morbidity and mortality. However, the molecular and genetic basis of CTD-PAH remains incompletely understood. This study aimed to screen for genetic defects in a cohort of patients with CTD-PAH, using a PAH-specific panel of 35 genes. During recruitment, 79 patients were studied, including 59 Systemic Sclerosis patients (SSc) and 69 females. Disease-associated variants were observed in nine patients: 4 pathogenic/likely pathogenic variants in 4 different genes (TBX4, ABCC8, KCNA5 and GDF2/BMP9) and 5 Variants of Unknown Significance (VUS) in 4 genes (ABCC8, NOTCH3, TOPBP1 and CTCFL). One patient with mixed CTD had a frameshift pathogenic variant in TBX4. Two patients with SSc-PAH carried variants in ABCC8. A patient diagnosed with Systemic Lupus Erythematous (SLE) presented a pathogenic nonsense variant in GDF2/BMP9. Another patient with SSc-PAH presented a pathogenic variant in KCNA5. Four patients with SSc-PAH carried a VUS in NOTCH1, CTCFL, CTCFL and TOPBP1, respectively. These findings suggest that genetic factors may contribute to Pulmonary Vascular Disease (PVD) in CTD patients.

Novel TNIP2 and TRAF2 Variants Are Implicated in the Pathogenesis of Pulmonary Arterial Hypertension.

Background: Pulmonary arterial hypertension (PAH) is a rare disease characterized by pulmonary vascular remodeling and right heart failure. Specific genetic variants increase the incidence of PAH in carriers with a family history of PAH, those who suffer from certain medical conditions, and even those with no apparent risk factors. Inflammation and immune dysregulation are related to vascular remodeling in PAH, but whether genetic susceptibility modifies the PAH immune response is unclear. TNIP2 and TRAF2 encode for immunomodulatory proteins that regulate NF-κB activation, a transcription factor complex associated with inflammation and vascular remodeling in PAH. Methods: Two unrelated families with PAH cases underwent whole-exome sequencing (WES). A custom pipeline for variant prioritization was carried out to obtain candidate variants. To determine the impact of TNIP2 and TRAF2 in cell proliferation, we performed an MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay on healthy lung pericytes transfected with siRNA specific for each gene. To measure the effect of loss of TNIP2 and TRAF2 on NF-kappa-beta (NF-κB) activity, we measured levels of Phospho-p65-NF-κB in siRNA-transfected pericytes using western immunoblotting. Results: We discovered a novel missense variant in the TNIP2 gene in two affected individuals from the same family. The two patients had a complex form of PAH with interatrial communication and scleroderma. In the second family, WES of the proband with PAH and primary biliary cirrhosis revealed a de novo protein-truncating variant in the TRAF2. The knockdown of TNIP2 and TRAF2 increased NF-κB activity in healthy lung pericytes, which correlated with a significant increase in proliferation over 24 h. Conclusions: We have identified two rare novel variants in TNIP2 and TRAF2 using WES. We speculate that loss of function in these genes promotes pulmonary vascular remodeling by allowing overactivation of the NF-κB signaling activity. Our findings support a role for WES in helping identify novel genetic variants associated with dysfunctional immune response in PAH.

Customized Massive Parallel Sequencing Panel for Diagnosis of Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension is a very infrequent disease, with a variable etiology and clinical expressivity, making sometimes the clinical diagnosis a challenge. Current classification based on clinical features does not reflect the underlying molecular profiling of these groups. The advance in massive parallel sequencing in PAH has allowed for the describing of several new causative and susceptibility genes related to PAH, improving overall patient diagnosis. In order to address the molecular diagnosis of patients with PAH we designed, validated, and routinely applied a custom panel including 21 genes. Three hundred patients from the National Spanish PAH Registry (REHAP) were included in the analysis. A custom script was developed to annotate and filter the variants. Variant classification was performed according to the ACMG guidelines. Pathogenic and likely pathogenic variants have been found in 15% of the patients with 12% of variants of unknown significance (VUS). We have found variants in patients with connective tissue disease (CTD) and congenital heart disease (CHD). In addition, in a small proportion of patients (1.75%), we observed a possible digenic mode of inheritance. These results stand out the importance of the genetic testing of patients with associated forms of PAH (i.e., CHD and CTD) additionally to the classical IPAH and HPAH forms. Molecular confirmation of the clinical presumptive diagnosis is required in cases with a high clinical overlapping to carry out proper management and follow up of the individuals with the disease.

Una respuesta ética en la atención a residencias de ancianos en la pandemia Covid-19 / An ethical response in the care of nursing homes in the covid-19 pandemic

La llegada de la pandemia COVID-19 puso en evidencia el riesgo de una posible falta de atención de los ancianos de las residencias de mayores. Aportamos la experiencia de un equipo multidisciplinar con profesionales voluntarios de diferentes especialidades que realizó una labor de apoyo a los profesionales sanitarios de las residencias. Este equipo se implementó desde las gerencias de atención primaria y de atención especializada. La sistemática de trabajo se inspiraba en el de hospitalización a domicilio e incluía la atención directa de los pacientes más complejos y el asesoramiento en las medidas de prevención, aislamiento e higiene dentro de la residencia. De este modo fue posible que los ancianos de las residencias con sospecha o diagnóstico de COVID-19 recibieran una atención adecuada por parte de un equipo interdisciplinar, que se descargara parte de la presión de los profesionales de las residencias y que los familiares percibieran que no existía abandono terapéutico. El compromiso desde diversos niveles asistenciales en una labor coordinada ha conseguido evitar que una población vulnerable pudiera quedar desatendido durante la pandemia

With the arrival of the COVID-19 pandemic, the risk of a possible lack of care for the elderly in nursing homes became evident. We summarize the experience of a multidisciplinary team with volunteer professionals from different specialties who carried out support for healthcare professionals in nursing homes. This team was implemented from both Primary and Specialty Care managements. Its work paradigm was proposed by our home hospitalization team, which included direct care of the most complex patients and general counselling on isolation, hygiene and preventive measures within the nursing homes. Thanks to this support, the elderly population placed there, with suspected or diagnosed COVID-19, received adequate care from an interdisciplinary team, which led part of the pressure to be released from their professional workers, and many family members were aware that there was no neglect of the elderly. Commitment from various levels of care in a coordinated effort has prevented a vulnerable population from being left unattended during the pandemic

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.