ABSTRACT
OBJECTIVE@#To investigate the clinical characteristics and genetic basis for a child with Keppen-Lubinsky syndrome (KPLBS).@*METHODS@#Trio-whole exome sequencing (Trio-WES) was carried out for the proband and her parents. Candidate variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The child has featured peculiar facies including large eyes, alar hypoplasia, microretrognathia, premature aging appearance in addition with growth delay and mental retardation. Trio-WES has identified that she has carried a de novo variant of the KCNJ6 gene, namely c.460G>C (p.Gly154Arg). The variant has not been recorded in the database. Prediction of protein structure indicated that the variant may affect the potassium ion selective filtration structure channel in the transmembrane region of KCNJ6 protein, which may result in up regulation of the function of the channel.@*CONCLUSION@#The de novo c.460G>C (p.Gly154Arg) variant of the KCNJ6 gene probably underlay the KPLBS in this child. Above finding has enriched the genotypic and phenotype spectrum of this syndrome.
Subject(s)
Female , Humans , Cataract , China , G Protein-Coupled Inwardly-Rectifying Potassium Channels/genetics , Hypogonadism/congenital , Intellectual Disability/genetics , Mutation , Exome SequencingABSTRACT
Objective. To describe food expenditure and consumption of foods prepared away from home among Mexican adults. Materials and methods. Data were from 45 241 adult participants in the National Health and Nutrition Survey 2006, a nationally-representative, cross-sectional survey of Mexican households. Descriptive statistics and multivariable linear and logistic regression were used to assess the relationship between location of residence, educational attainment, socioeconomic status and the following: 1) expenditure on all food and at restaurants, and 2) frequency of consumption of comida corrida or restaurant food and street food. Results. Food expenditure and consumption of food prepared away from home were positively associated with socioeconomic status, educational attainment, and urban vs. rural residence (p<0.001 for all relationships in bivariate analyses). Conclusions. Consumption of food prepared outside home may be an important part of the diet among urban Mexican adults and those with high socioeconomic status and educational attainment.
Objetivo. Describir los gastos en alimentos y el consumo de alimentos preparados fuera de casa en población mexicana. Material y métodos. Los datos fueron de 45 241 adultos mexicanos en la Encuesta Nacional de Salud y Nutrición de 2006, representativa al nivel nacional. Se utilizaron estadísticas descriptivas y regresión linear y logística para estimar la relación entre el lugar de residencia, el nivel educativo y el nivel socioeconómico, con el gasto en todos los alimentos y en restaurantes, y con la frecuencia de consumo de comida corrida, en restaurantes y de la calle. Resultados. El gasto en alimentos y el consumo de alimentos preparados se asociaron positivamente con el nivel socioeconómico, el nivel educativo y la residencia rural (p<0,001 para todas las relaciones). Conclusiones. El consumo de alimentos preparados puede ser una parte importante de la dieta de los adultos urbanos y de aquéllos con altos niveles socioeconómicos y educativos.
Subject(s)
Animals , Cricetinae , Female , Humans , Male , Mice , G Protein-Coupled Inwardly-Rectifying Potassium Channels/chemistry , Neurodegenerative Diseases/pathology , Spinal Cord/metabolism , Tyrosine/chemistry , DNA , Anisomycin/chemistry , Antibodies/chemistry , Behavior , Blotting, Western , CHO Cells , Cell Line , Cell Line, Tumor , Dose-Response Relationship, Drug , Electrophysiology , Enzyme-Linked Immunosorbent Assay , G Protein-Coupled Inwardly-Rectifying Potassium Channels/physiology , GTP-Binding Proteins/metabolism , Heart Atria/metabolism , Heart Ventricles/cytology , Heart Ventricles/pathology , Immunoblotting , Immunohistochemistry , Inflammation , Microscopy, Confocal , Microscopy, Fluorescence , Muscle Cells/metabolism , Neurons/metabolism , Phosphorylation , Plasmids/metabolism , Protein Structure, Tertiary , Sciatic Nerve/metabolism , Spinal Cord/pathology , Stress, Physiological , Xenopus laevisABSTRACT
Objetivo. Explicar la variación de la desnutrición infantil (DI), entendida como baja talla para la edad (0 a 5 años) entre 1999 y 2006. Material y métodos. Se emplearon estimaciones estatales de DI y diversos indicadores que reflejan las probables causas subyacentes del fenómeno como la pobreza, el producto per cápita estatal, la educación de las mujeres y los accesos a infraestructura de salud y de drenaje. Para el análisis de datos se utilizaron los métodos de regresión con datos panel de efectos fijos y aleatorios. Resultados. Se encontró que la carencia de salud y drenaje, así como la pobreza, empeoran la DI, mientras que la educación de las mujeres la disminuye. Conclusiones. El estudio muestra que las variables de infraestructura explican en buena parte la variación reciente de la DI entre estados, y que el crecimiento económico no es una condición suficiente para reducir la DI.
Objective. Explain the variation in child malnutrition (CM), understood as low height for age (0 to 5 years old) for the period 1999-2006. Materials and methods. State estimations of child malnutrition and several indicators of subjacent probable causes of CM were employed, such as poverty indices, state product per capita, women scholar attainment and access to health and the sewage system. Panel data regression analysis with fixed and random effects were used to analyze the data. Results. The results indicate that the lack to access to health and sewage systems and poverty worsen CM, whereas women education helps to diminish CM. Conclusion. The study shows that infrastructure variables explain a significant part of the recent variation in DI across Mexican states, and that economic growth is not a sufficient condition to diminish DI.
Subject(s)
Animals , Male , Mice , Brain/metabolism , G Protein-Coupled Inwardly-Rectifying Potassium Channels/biosynthesis , G Protein-Coupled Inwardly-Rectifying Potassium Channels/genetics , Neurons/metabolism , Baclofen/pharmacology , Brain/drug effects , Dose-Response Relationship, Drug , In Vitro Techniques , Mice, Knockout , Neurons/drug effects , Neurons/ultrastructureABSTRACT
<p><b>OBJECTIVE</b>To investigate the prevalence of KCNJ5 gene missense mutations and their role in patients with unilateral adrenal hyperplasia (UAH).</p><p><b>METHODS</b>Fourteen UAH tissues were collected through surgical resection, and all the tissues were confirmed by pathology. Peripheral blood samples of the same patients were collected as control. The coding regions of the KCNJ5 were detected by direct DNA sequencing. Protein structure and function were predicted with specific software.</p><p><b>RESULTS</b>Three missense mutations were detected among the 14 patients with UAH, which included c.451G>C/A (p.G151R) (2/14), c.503T>G (p.L168R) (1/14), c.830T>A (p.S209T) (9/14). Among these, c.830T>A is a newly identified somatic mutation. Protein structure prediction showed that S209T lied in the second transmembrane domain, a conservation region of KCNJ5. S209 was also the phosphorylation site of PKC that is located in intracellular area.</p><p><b>CONCLUSION</b>Missense mutations of KCNJ5 gene may be associated with UAH. Protein structure prediction has suggested that KCNJ5 mutations may be associated with UAH.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Adrenal Hyperplasia, Congenital , Genetics , Amino Acid Sequence , G Protein-Coupled Inwardly-Rectifying Potassium Channels , Genetics , Molecular Sequence Data , Mutation, Missense , Sequence Analysis, DNAABSTRACT
<p><b>OBJECTIVE</b>To identify the effect of ethanol and its metabolite acetaldehyde on acetylcholine-sensitive K(+) channel Kir3.1 protein expression, and explore the potential role of this channel and acetaldehyde in arrhythmia caused by acute alcoholic intoxication.</p><p><b>METHODS</b>Primary atrial cardiomyocytes were isolated from 150 newborn SD rats by typsin and type II collagenase, cultured and troponin I was determined by immunofluorescence. Cell survival in 200-800 mmol/L ethanol or 50-500 µmol/L acetaldehyde treated cells for 24 hours was measured by CCK-8 assay to determine the concentration of ethanol and acetaldehyde for inducing apoptosis in cardiomyocytes. The highest non-apoptotic concentration (200 mmol/L) of ethanol and acetaldehyde (100 µmol/L) was used in the main study. Kir3.1 protein expression was detected by Western blot.</p><p><b>RESULTS</b>(1) Cellular immunofluorescence results showed that cultured cells are cardiomyocytes, and more than 90% of these cells are troponin I positive. (2) CCK-8 assay demonstrated that the survival rate of cardiomyocytes in the groups treated by ethanol over 400 mmol/L for 24 hours or acetaldehyde over 400 µmol/L was significantly lower than that of the control group (P < 0.05), while the survival rate was similar in cardiomyocytes treated by ethanol less than 200 mmol/L or acetaldehyde less than 350 µmol/L for 24 hours and the control group (P > 0.05). (3) Western-bolt assay revealed that ethanol and acetaldehyde treatment for 24 hours upregulated Kir3.1 protein expression in primary atrial cardiomyocytes of newborn SD rats by (44.52 ± 23.07)% and (45.04 ± 22.01)% respectively compared with the control group (all P < 0.01).</p><p><b>CONCLUSIONS</b>Acute ethanol and acetaldehyde treatment could significantly upregulate the protein expression of acetylcholine-sensitive K(+) channel Kir3.1, this might serve as a potential mechanism for arrhythmia caused by acute alcoholic intoxication.</p>
Subject(s)
Animals , Rats , Acetaldehyde , Metabolism , Acetylcholine , Alcoholic Intoxication , Metabolism , Apoptosis , Cells, Cultured , Ethanol , Pharmacology , G Protein-Coupled Inwardly-Rectifying Potassium Channels , Heart Atria , Myocytes, Cardiac , Rats, Sprague-Dawley , SincalideABSTRACT
Introduction: Tuberculosis is a common opportunistic infection in renal transplant patients. Objective: To obtain a clinical and laboratory description of transplant patients diagnosed with tuberculosis and their response to treatment during a period ranging from 2005 to 2013 at the Pablo Tobón Uribe Hospital. Methods: Retrospective and descriptive study. Results: In 641 renal transplants, tuberculosis was confirmed in 12 cases. Of these, 25% had a history of acute rejection, and 50% had creatinine levels greater than 1.5 mg/dl prior to infection. The disease typically presented as pulmonary (50%) and disseminated (33.3%). The first phase of treatment consisted of 3 months of HZRE (isoniazid, pyrazinamide, rifampicin and ethambutol) in 75% of the cases and HZME (isoniazid, pyrazinamide, moxifloxacin and ethambutol) in 25% of the cases. During the second phase of the treatment, 75% of the cases received isoniazid and rifampicin, and 25% of the cases received isoniazid and ethambutol. The length of treatment varied between 6 and 18 months. In 41.7% of patients, hepatotoxicity was associated with the beginning of anti-tuberculosis therapy. During a year-long follow-up, renal function remained stable, and the mortality rate was 16.7%. Conclusion: Tuberculosis in the renal transplant population studied caused diverse nonspecific symptoms. Pulmonary and disseminated tuberculosis were the most frequent forms and required prolonged treatment. Antituberculosis medications had a high toxicity and mortality. This infection must be considered when patients present with a febrile syndrome of unknown origin, especially during the first year after renal transplant. .
Introdução: A tuberculose é uma infecção oportunista comum em pacientes transplantados renais. Objetivo: Oferecer uma descrição clínica e laboratorial de pacientes transplantados com diagnóstico de tuberculose e sua resposta ao tratamento durante o período entre 2005 e 2013 no Hospital Pablo Tobón Uribe. Métodos: Estudo retrospectivo descritivo. Resultados: Em 641 transplantes renais, a tuberculose foi confirmada em 12 pacientes. Destes, 25% tinham histórico de rejeição aguda e 50% apresentaram níveis de creatinina superiores a 1,5 mg/dl antes da infecção. A patologia geralmente se apresentava como pulmonar (50%) e disseminada (33,3%). A primeira fase do tratamento consistiu de três meses de HZRE (isoniazida, pirazinamida, rifampicina e etambutol) em 75% dos casos e HZME (isoniazida, pirazinamida, moxifloxacina e etambutol) em 25% dos pacientes. Durante a segunda fase do tratamento, 75% dos pacientes receberam isoniazida e rifampicina e 25% isoniazida e etambutol. A duração do tratamento variou entre seis e 18 meses. Em 41,7% dos pacientes, hepatotoxicidade foi associada ao início do tratamento da tuberculose. Durante o seguimento de um ano a função renal manteve-se estável e a taxa de mortalidade foi de 16,7%. Conclusão: A tuberculose foi responsável por diversos sintomas inespecíficos na população de transplantados renais estudada. Tuberculose pulmonar e disseminada foram as formas mais frequentes de acometimento e necessitaram de tratamento prolongado. Medicamentos contra a tuberculose apresentaram alta toxicidade e mortalidade. Esta infecção deve ser considerada quando o paciente apresenta síndrome febril de origem desconhecida, especialmente durante o primeiro ano após o transplante renal. .
Subject(s)
Animals , Female , Male , Mice , Locus Coeruleus/drug effects , Narcotics/pharmacology , Neural Inhibition/drug effects , Neurons/drug effects , Potassium Channels/metabolism , Barium/pharmacology , Calcium/metabolism , Enkephalin, Methionine/pharmacology , G Protein-Coupled Inwardly-Rectifying Potassium Channels , GTP-Binding Proteins/metabolism , Heterozygote , Homozygote , Ion Channel Gating/drug effects , Ion Channel Gating/physiology , Locus Coeruleus/cytology , Locus Coeruleus/physiology , Mice, Knockout , Membrane Potentials/drug effects , Membrane Potentials/physiology , Neural Inhibition/physiology , Neurons/physiology , Patch-Clamp Techniques , Protein Subunits , Potassium Channel Blockers/pharmacology , Potassium Channels, Inwardly Rectifying/antagonists & inhibitors , Potassium Channels, Inwardly Rectifying/deficiency , Potassium Channels, Inwardly Rectifying/genetics , Potassium Channels, Inwardly Rectifying/metabolism , Potassium Channels/deficiency , Potassium Channels/geneticsABSTRACT
<p><b>OBJECTIVE</b>To assess the association of polymorphisms of G protein-coupled inwardly-rectifying potassium channels 4 (GIRK4) gene with essential hypertension in ethnic Uygurs from southern Xinjiang.</p><p><b>METHODS</b>A total of 1194 (461 males and 733 females) Uygur residents aged 30 to 70 and with a body mass index (BMI) over 18.5 kg/m(2) were selected from Hetian region. All of the subjects have received questionnaire survey, physical examination, biochemical analysis and blood pressure measurement. They were divided into hypertensive group and normotensive group. Genotyping by the TaqMan polymerase chain reaction method was performed for 4 common single nucleotide polymorphisms (rs4937391, rs2604204, rs6590357 and rs1122149), and a case-control study was carried out.</p><p><b>RESULTS</b>Genotype distributions of rs4937391, rs2604204, rs6590357 and rs1122149 in both groups were in Hardy-Weinberg equilibrium (P> 0.05). The average systolic blood pressure of CC genotype of rs11221497 single nucleotide polymorphism (SNP)[(132.69± 26.9) mmHg)] was higher than the CG genotype [(127.4± 22.7) mmHg] and GG genotype [(121.1± 26.3) mmHg]. There has a significantly difference in average systolic and diastolic blood pressures between CC and GG genotypes (P< 0.05). A case-control association analysis revealed that the rs11221497 SNP was in association with essential hypertension with the dominant model [P< 0.05, OR= 0.67 (0.49-0.93)]. Haplotype analysis indicated that H6(C-G-C-G) was significantly more common in normotensive group than hypertensive group (P= 0.001).</p><p><b>CONCLUSION</b>The rs11221497 SNP of the GIRK4 gene is associated with essential hypertension in ethnic Uygur population in Xinjiang.</p>
Subject(s)
Female , Humans , Male , Asian People , Genetics , Case-Control Studies , Essential Hypertension , G Protein-Coupled Inwardly-Rectifying Potassium Channels , Genetics , Genetic Predisposition to Disease , Hypertension , Genetics , Obesity , Genetics , Polymorphism, Single NucleotideABSTRACT
<p><b>OBJECTIVE</b>To assess the association between polymorphisms of rs3740835(C/A) and rs2604204(A/C) in KCNJ5 gene with the susceptibility to unilateral and bilateral primary aldosteronism (PA).</p><p><b>METHODS</b>A total of 1043 subjects were studied, which included 83 unilateral PA patients,142 bilateral PA patients and 818 essential hypertensive(EH) patients. The polymorphism of KCNJ5 gene at rs3740835(C/A) and rs2604204(A/C) position were analyzed with a TaqMan genotyping technique.</p><p><b>RESULTS</b>Frequencies of A allele and AA+AC genotype at rs3740835(C/A) in unilateral PA group were significantly higher than EH group (P < 0.05). However, the above frequencies did not show a statistical significance between bilateral PA group and EH group (P > 0.05). No statistical difference was detected in the distribution of alleles or genotypes at rs2604204 (A/C) between unilateral PA and EH group or between bilateral PA and EH group. Haplotypic frequencies of C-A and A-A in unilateral PA group were significantly higher and lower than EH group, respectively. However, there was no statistical difference in the haplotype distribution between bilateral PA and EH groups.</p><p><b>CONCLUSION</b>Rs3740835(C/A) polymorphism may be associated with unilateral PA but not with bilateral PA. rs2604204(A/C) polymorphism is not associated with either unilateral or bilateral PA. Haplotype C-A and A-A may respectively be susceptibility factor and protective factor for unilateral PA. No haplotype has been found to associate with bilateral PA.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , G Protein-Coupled Inwardly-Rectifying Potassium Channels , Genetics , Haplotypes , Hyperaldosteronism , Genetics , Polymorphism, GeneticABSTRACT
G protein-coupled inward rectifier K(+) channel 4(GIRK4) is a G protein-coupled inward rectifier potassium channel family member. Encoded by the KCNJ5, it is widely distributed in the mammalian heart, brain, and other tissues and organs. Recent studies have demonstrated that the abnormal expression of GIRK4 gene is associated with atrial fibrillation, and meanwhile may be closely related to obesity, metabolic syndrome, and many other clinical conditions. Further research on the role the GIRK4 gene in the pathophysiology of these clinical conditions will definitely facilitate their clinical diagnosis and treatment.
Subject(s)
Humans , Atrial Fibrillation , Genetics , G Protein-Coupled Inwardly-Rectifying Potassium Channels , Genetics , Metabolic Syndrome , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To assess the association between polymorphisms of protein-activated inwardly rectifying K+ channel (GIRK4) gene and insulin resistance (IR) in Xinjiang Uygur population.</p><p><b>METHODS</b>A cross-sectional epidemiological survey-based case-control study was carried out, for which 1295 subjects (including 324 IR patients and 971 non-IR controls) were randomly selected. Functional region of the GIRK4 gene was sequenced for 48 randomly selected IR patients. Representative variable sites were chosen, with its association with IR assessed in 1295 Uygur subjects.</p><p><b>RESULTS</b>rs11221497 variant was associated with IR in Uygur subjects under 50 years old (P=0.017 in genotype model, P=0.009 in dominant model). Subjects with dominant model of CC genotype have an OR of 1.833 (95%CI: 1.157-2.905) for IR.</p><p><b>CONCLUSION</b>GIRK4 gene polymorphisms may be associated with IR in Uygur ethnics from Xinjiang. The CC genotype of rs11221497 variant is a risk factor for IR.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Alleles , Case-Control Studies , G Protein-Coupled Inwardly-Rectifying Potassium Channels , Genetics , Gene Frequency , Genetic Predisposition to Disease , Genotype , Insulin Resistance , Genetics , Polymorphism, Single Nucleotide , Risk FactorsABSTRACT
Considerable evidences have indicated the differences between different sexes in their pain responses and opioid antinociception in which Opioids have been more potent in males than females. GIRK[2], the primary post-synaptic effectors of opioids in the CNS, possibly contributes in these sex-related differences. In the present study, we examined the role and effect of gonadal steroid hormones on GIRK[2] gene transcription in rats. Male and female Wistar rats were divided into four groups of intact infant or adult, GDX, sham and GDX+T groups. "semiquantitave RT-PCR" was used to determine the GIRK[2] gene expression in spinal cord tissue of the rats. Our results showed that in the spinal cord of male rats, gene transcription of infant group did not fluctuate along with expression level of this gene in GDX or adult intact groups. Elimination of gonadal hormones in male rats significantly decreased the expression level of GIRK2 gene. These changes were not restored by testosterone replacement. However, in females, a greater expression of GIRK[2] gene was found in intact adult or GDX rats than those of infants. Ovariectomy of animals failed to alter the GIRK2 mRNA level. No significant preferential differences were observed in GIRK[2] gene transcription between both sexes of intact, sham and infant groups. These findings show that regulation of GIRK[2] gene transcription by gonadal hormones is male-dominant. Whereas, other sex-dependent developmental factors prominently affect on GIRK[2] gene transcription in female animals. Further investigations are needed to clarify the exact mechanism