RESUMO
We conducted a hospital-based case-control study in Korea to investigate whether apoptosis- and cell cycle control-related genes are associated with childhood brain tumor. Incident brain tumor cases (N = 70) and non-cancer controls (N = 140), frequency-matched by age and gender, were selected from 3 teaching hospitals in Seoul between 2003 and 2006. Tag single nucleotide polymorphisms (SNPs) (N = 297) in 30 genes related to apoptosis and cell cycle control were selected using a pairwise linkage-disequilibrium-based algorithm. Five tag SNPs in 2 genes (AICDA and CASP14) remained significant after adjusted multiple tests. The most significant association with childhood brain tumor risk was for IVS1-401G>C in the AICDA gene [odds ratio (OR) = 2.8; 95% confidence interval (95%CI) = 1.25-6.46]; the polymorphism *9276A>C of CASP14 was associated with decreased brain tumor risk (OR = 0.4; 95%CI = 0.19-0.95). We concluded that genetic polymorphisms in AICDA and CASP14 are associated with risk for brain tumor in Korean children.
Assuntos
Neoplasias Encefálicas/genética , Caspases/genética , Citidina Desaminase/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Apoptose/genética , Ciclo Celular/genética , Criança , Pré-Escolar , Feminino , Humanos , Masculino , República da Coreia , Fatores de RiscoRESUMO
Children with suspected respiratory syncytial virus infection were examined prospectively in a randomized evaluation of standard ribavirin aerosol therapy (6 gm/300 ml water for 18 hours daily) compared with high-dose, short-duration ribavirin aerosol therapy (6 gm/100 ml water given for a period of 2 hours three times a day) by means of an oxygen hood (n = 20) or a ventilator (n = 12). Viral shedding was quantitated daily; clinical observations were recorded daily by 2 physicians aware and one unaware of treatment assignments. Study characteristics evaluated at entry were not significantly different in the high-dose and the standard-dose groups. Viral titers and clinical scores decreased similarly in both groups during the study; pulmonary function test results were also similar at discharge in children not receiving mechanical ventilation. Potential complications related to aerosol therapy were noted in three patients (one hood patient who was receiving standard therapy; two patients with an endotracheal tube in place who were receiving high-dose therapy); substantial crystallization was noted in the tubing of the patients undergoing intubation and receiving high-dose therapy. Environmental sampling revealed that ribavirin was nearly undetectable near patients supported by mechanical ventilation who were receiving either form of therapy, and was significantly decreased on a daily basis in patients without an endotracheal tube who were receiving high-dose therapy compared with those receiving standard therapy. The effects of high-dose, short-duration aerosol ribavirin therapy were similar to those of standard-dose therapy in our study patients and resulted in a decreased release of ribavirin into the room of patients receiving therapy by means of an oxygen hood.
Assuntos
Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Ribavirina/administração & dosagem , Aerossóis , Microbiologia do Ar , Criança , Pré-Escolar , Esquema de Medicação , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Oxigenoterapia/instrumentação , Infecções por Vírus Respiratório Sincicial/terapia , Vírus Sinciciais Respiratórios/isolamento & purificação , Resultado do TratamentoRESUMO
Apolipoprotein A-IV (apoA-IV, protein; APOA4, gene) is a major constituent of high-density lipoprotein (HDL) and triglyceride-rich lipoprotein particles, but its precise function in lipid metabolism is still uncertain. We have determined APOA4 genetic polymorphism in 285 randomly selected Melanesians from the Solomon Islands and have evaluated its significance in lipid metabolism. By using isoelectric focusing and immunoblotting techniques, a variant pattern, indistinguishable from the APOA4*2 allele uniquely found in white populations at a frequency of about 8%, was detected at a relatively high frequency (19%) in the Melanesian sample. Polymerase chain reaction (PCR) amplification and DNA sequencing of the 3' end of the APOA4 gene revealed that the Melanesian mutation is distinct from the known APOA4*2 mutation and that it involves a four-amino acid deletion in the evolutionarily conserved carboxyl-terminal region in the apoA-IV protein, which consists of four repeats of four amino acids each. After adjustment for concomitant variables, we investigated the impact of the deletion polymorphism on plasma levels of cholesterol, triglycerides, apoA-I, apoA-II, and apoE. A significant (P = .02) and gene-dosage effect was observed on the plasma levels of apoA-I and apoA-II: these levels were lowest in individuals homozygous for the deletion allele (D), intermediate in heterozygotes (ND), and highest in homozygous individuals for the normal allele (N). The average effect of the APOA4*D allele was to lower apoA-I and apoA-II by 8 mg/dL and 2 mg/dL, respectively, and the APOA4 polymorphism accounted for about 3% of the phenotypic variance in both cases.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Apolipoproteínas A/genética , Deleção de Genes , Metabolismo dos Lipídeos , Polimorfismo Genético , Alelos , Sequência de Bases , Genótipo , Humanos , Pessoa de Meia-Idade , Dados de Sequência Molecular , FenótipoRESUMO
The purpose of this work was to examine the influence of apolipoprotein gene variation on plasma lipid levels in a population of Mayan Indians of the Yucatán Peninsula, Mexico. Four restriction enzymes: XmnI, PstI, SstI, and PvuII, were used to detect restriction fragment length polymorphisms (RFLP) within the region of the apolipoprotein AI/CIII/AIV gene cluster. The frequencies of these polymorphisms in this Mayan population were similar to those reported for other Amerindian populations, but differed widely from those reported for Caucasian populations. The XmnI and SstI RFLPs were informative for association studies in this population, and we analyzed their influence on the quantitative variation of plasma cholesterol and triglycerides. Using a nonparametric analysis of variance, it is shown that the presence of the XmnI restriction site had a significant effect in lowering plasma cholesterol, whereas the presence of the restriction site for SstI had a significant effect in raising plasma triglycerides. Consequently, genetic indicators of both low and high risk for lipid-related diseases, such as atherosclerosis and coronary heart disease, seem to be present within the same gene region in this Mayan population.