RESUMO
The objective of this investigation was to analyze possible association between BclI polymorphism of glucocorticoid receptor gene and obesity in patients with bronchial asthma (BA). The study involved 188 patients with bronchial asthma and 95 apparently healthy adult individuals. Generally accepted assessments and examinations for BA diagnosis, and anthropometric, molecular-genetic and statistic methods of investigation were used in the research. It was found out that the patients with BA demonstrated higher body mass index (BMI) and higher ratio of fat centralization much more often, than the control group. Genotypes distribution for BclI polymorphism in patients with BA showed a statistically significant difference between patients with different BMI unlike the control group. Comparison of genotype frequency for BclI polymorphism in glucocorticoid receptor gene in individuals with different ratio of fat centralization in the control group and in the patients with BA separately showed statistically significant differences in the distribution of gene allelic variations only among the patients with BA. It was demonstrated that G/G genotype in the patients with visceral obesity was associated with BA.
Assuntos
Asma/genética , Desoxirribonucleases de Sítio Específico do Tipo II/química , Obesidade/genética , Polimorfismo de Fragmento de Restrição , Receptores de Glucocorticoides/genética , Adulto , Alelos , Asma/complicações , Asma/metabolismo , Asma/patologia , Distribuição da Gordura Corporal , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/metabolismo , Obesidade/patologia , Receptores de Glucocorticoides/metabolismoRESUMO
The article analyses the results of investigating the connection between BCL1-polymorphism of glucocorticoid receptor gene and respiratory diseases. Its role in increasing sensitivity to glucocorticoids is proved here. The authors investigated the association of Bcl1 polymorphism with predisposition to bronchial asthma, chronic obstructive pulmonary disease, with the nicotine addiction degree and with progressing disorders of pulmonary function in cystic fibrosis.
Assuntos
Asma/genética , Fibrose Cística/genética , Polimorfismo de Nucleotídeo Único , Doença Pulmonar Obstrutiva Crônica/genética , Receptores de Glucocorticoides/genética , Alelos , Asma/tratamento farmacológico , Asma/metabolismo , Asma/fisiopatologia , Fibrose Cística/tratamento farmacológico , Fibrose Cística/metabolismo , Fibrose Cística/fisiopatologia , Progressão da Doença , Expressão Gênica , Frequência do Gene , Predisposição Genética para Doença , Glucocorticoides/uso terapêutico , Humanos , Pulmão/metabolismo , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Fatores de Risco , Tabagismo/fisiopatologia , Tabagismo/psicologiaRESUMO
The aim of our study was to investigate frequencies of alleles and genotypes of Bcl1 GR gene polymorphism and their correlation with prevalence of BA. Study involved 188 patients with BA and 95 healthy individuals. Bcl1 (rs41423247) polymorphism in exon 2 was determined by means of polymerase chain reaction with subsequent RFLP analysis (restriction fragment length polymorphism) by Fleury I. et al. with modifications. Statistical analysis of the results was performed using SPSS-17 program. The results showed statistically significant differences in genotypes distribution of BclI polymorphism of GR gene in the control group and in patients with BA. The frequency of genotypes distribution of Bcl1 polymorphism of GR gene in controls: C/C, C/G, G/G - 0,421/ 0,453/0,126; in patients with bronchial asthma: 0.228/0.426/0.346, respectively (p=0.001). It was found out that G/G-homozygotes have a fivefold higher risk of BA than those homozygous for C/C regardless of gender. We demonstrated that BA risk in females, homozygous for the minor allele, is higher (p=0.016) and men with G/G genotype of Bcl1 GR gene polymorphism have the highest risk of BA. Thus, G/G genotype of Bcl1 polymorphism of the glucocorticoid receptor gene is associated with the development of asthma.
Assuntos
Asma/genética , Predisposição Genética para Doença , Polimorfismo de Fragmento de Restrição/genética , Receptores de Glucocorticoides/genética , Asma/patologia , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Homozigoto , Humanos , MasculinoRESUMO
The article provides modern information about the structure of glucocorticoid receptor gene and its isoforms, the most common variants of missens and allelic polymorphisms. The polymorphisms N363S, BclI, ER22/23EK and TthIIII were characterized. The relationship of these polymorphisms with physique and metabolic changes, cardiovascular system diseases as well as with sensitivity to glucocorticoids (GCS) was analyzed. It has been established that N363S and BclI polymorphisms are associated with hypersensitivity to corticosteroids and can be the predictors of obesity, metabolic syndrome, and polymorphisms ER22/23EK and TthIIII are associated with resistance to GC and favorable metabolic profile.
