RESUMO
Atherosclerotic and its cardiovascular complications are responsible for 17.5 million deaths a year, according to the World Health Organization. There is consensus that atherosclerosis involves multiple pathogenic processes initiated by endothelial dysfunction, with inflammation and vascular proliferation determining alterations in the matrix, with consequent formation of the atheromatous plaque and its clinical implications. Risk factors such as hypertension, diabetes mellitus, dyslipidemia, and smoking are widely known. Currently, genotyping, which is not directly related to these factors, is not accepted to estimate the risk of cardiovascular diseases, but strong evidence indicates several polymorphic genes as factors of risk and progression leading to complications of the disease. Among the genes involved, eNOS (endothelial nitric oxide synthase gene), which is responsible for the production of endothelial nitric oxide (an important arterial vasodilator), when presented in polymorphic variation can determine production, malfunction, and predisposition to atherosclerosis. In the present study, we analyzed the G894T polymorphism of the eNOS gene in groups of individuals diagnosed with atherosclerosis and in a control group. We collected 200 blood samples from patients previously diagnosed with atherosclerosis and 100 samples formed the control group. The genotyping analysis for polymorphism of the eNOS gene was determined by PCR. We considered variables such as gender, smoking, smoking history, and alcohol consumption; statistical differences were found in the distribution of case and control groups (P = 0.0378) and in non-smoking patients (P = 0.0263). In the other associations, no statistically significant difference was found. In the population studied, the frequency of the heterozygous genotype (GT) was much higher than in the other populations (GG and TT) in both groups (case and control). The GG genotype showed greater susceptibility to atherosclerosis. Association of the GG genotype in non-smokers also showed greater susceptibility. Gender, alcohol consumption, smoking, and smoking history did not influence atherosclerosis.
Assuntos
Aterosclerose/genética , Óxido Nítrico Sintase Tipo III/genética , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Feminino , Genótipo , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Mutação de Sentido IncorretoRESUMO
Atherosclerosis is characterized by lesions, called atheroma or atheromatous plaques, in the inner layer of blood vessels, which block the vascular lumen and weaken the underlying tunica media. Several modifiable and non-modifiable risk factors for the development of atherosclerosis exist. The modifiable risk factors include hypertension, smoking, obesity, high LDL and low HDL cholesterol levels, sedentary lifestyle, and stress; the non-modifiable factors include diabetes mellitus, family history of hypertension and heart disease, thrombophilia, sex, age, and genetic factors. The association of polymorphisms in GST with coronary artery disease has been studied since the polymorphisms can affect enzyme activity and contribute to the onset of atherosclerosis. We analyzed polymorphisms in GSTM1 in individuals diagnosed with atherosclerosis as well as in healthy individuals (control group). The frequency of the GSTM1 present genotype in the atherosclerosis group was 1.2 times higher than that observed in the control group. We found no sex- or alcohol-consumption-dependent differences between the occurrences of the present and null genotypes. However, the GSTM1 present genotype occurred in 52.6% individuals with atherosclerosis who reported smoking 20 or more cigarettes per day and in 60% individuals who smoked 10 to 20 cigarettes per day (P = 0.0035). In addition, the GSTM1 present genotype was more frequent in individuals who reported being former smokers - 45.5% in individuals with atherosclerosis who smoked for more than 20 years and 50% each for individuals in the control group who smoked for less than 10 years or for 10 to 20 years, respectively (P = 0.0240).
Assuntos
Aterosclerose/genética , Aterosclerose/patologia , Glutationa Transferase/genética , Polimorfismo Genético , Fumar/patologia , Aterosclerose/epidemiologia , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fumar/epidemiologiaRESUMO
Many environmental agents affect the development of male germ cells at different stages. Apoptosis is common during normal spermatogenesis; it plays an important role in controlling the number of germ cells and the disposal of defective stem cells to produce functional sperm. The presence of p53 in primary spermatocytes suggests that it plays a role in the prophase of meiosis. p53 is expressed in the testis in both spermatocytes and spermatogonia. This suggests that the p53 gene (TP53) is important for apoptosis regulation during spermatogenesis, and may be associated with male infertility. The main causes of male infertility are genetic, physical, and pathological abnormalities, intense and prolonged exercise, aging, drug use, and long periods of sexual abstinence. Approximately 20% of male infertility is idiopathic. The Trp53 gene is involved in meiosis in male rats and mice suggesting that the p53 plays a critical role in spermatogenesis. We investigated the association between the TP53 polymorphism in codon 72 and idiopathic male infertility in 208 semen samples: 106 showed abnormal semen analysis results and were from infertile men, and 102 were from fertile individuals (the control group). Changes in Trp53 expression are associated with the main phase regulating meiotic progression with a peak in the pachytene stage, and Trp53-deficient mice exhibit degenerative syndrome (giant cells). The genotypic and allelic frequencies were not significantly different among the groups in this study; the results suggest that the TP53 polymorphism in codon 72 is not associated with the pathogenesis of idiopathic male infertility or failure of spermatogenesis.
Assuntos
Códon/genética , Infertilidade Masculina/genética , Polimorfismo Genético , Proteína Supressora de Tumor p53/genética , Eletroforese em Gel de Ágar , Frequência do Gene/genética , Humanos , Masculino , Reação em Cadeia da PolimeraseRESUMO
The aim of this study was to determine the prevalence of polymorphisms in the glutathione S-transferase genes GSTM1 and GSTT1 in patients with lens opacity (cataract). Peripheral blood samples were obtained from male and female patients (N = 23) with cataract. The GSTM1 and GSTT1 polymorphic regions were amplified by polymerase chain reaction, and the amplification products were electrophoresed on a 2% agarose gel. The obtained bands were by staining with ethidium bromide. The results were compared by a chi-square test using the BioEstat software (v.5.0). The frequencies of the GSTM1- and GSTT1-null genotypes were higher than those of the GSTM1- and GSTT1-present genotypes. The frequency of GSTT1-null genotypes was approximately 1.7 times higher than that of GSTM1, which was a statistically significant difference (P = 0.0019). Although a consensus remains to be reached on the correlation between genetic polymorphisms in GSTs and cataract susceptibility, the observations from most scientific studies are similar to those reported in this study. Thus, we conclude that the absence of these genes, particularly GSTT1, is correlated with the development of lens opacity.
Assuntos
Catarata/diagnóstico , Catarata/genética , Predisposição Genética para Doença , Glutationa Transferase/genética , Polimorfismo Genético , Adulto , Catarata/patologia , Feminino , Expressão Gênica , Frequência do Gene , Glutationa Transferase/deficiência , Humanos , Cristalino/metabolismo , Cristalino/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
The first reports about pterygium date back to Hippocrates, and this disease still threatens vision health around the world. Pterygium is a formation of fibrous tissue consisting of highly vascularized epithelial and subepithelial tissue that grows excessively and with an abnormal shape on the cornea. Many physical and biological factors are associated with the pathogenesis of pterygium, including heat, dust, and other particles in the atmosphere, and immunological mechanisms, mechanisms involving extracellular matrix reorganization, growth factors, cytokines, apoptosis, and angiogenesis. The aim of this study was to further investigate the association between polymorphisms in GSTM1 and the formation of pterygium. We collected peripheral blood samples from 90 patients diagnosed with pterygium and from 23 subjects with-out the disease in order to perform molecular analysis of the GSTM1 gene. Subjects with one or two copies of the GSTM1 allele had a normal genotype while those without any copies of the allele had a null geno-type. The chi-square test or the Fisher exact test was performed in order to investigate possible associations between the molecular analysis and the risk of pterygium. A significant difference between the frequency of the GSTM1-null genotype in patient and control groups was identified. However, sub-group analysis found that the GSTM1-null genotype was statistically significant in men, but not in women, and in Caucasians, but not in Brown or Black groups. Furthermore, the GSTM1-null geno-type was not related to any of the risk factors analyzed: cases in family, occupational exposure, smoking, hypertension, and diabetes.
Assuntos
Glutationa Transferase/genética , Polimorfismo Genético , Pterígio/etnologia , Pterígio/genética , População Branca/genética , Brasil/etnologia , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Fatores SexuaisRESUMO
Pterygium is an inflammatory and degenerative ocular surface disease in which the conjunctiva on the cornea grows to form a fibrous tissue in the shape of a triangle. The disorder may be characterized by cell proliferation, inflammatory processes, fibrosis, angiogenesis, and destruction of the extracellular matrix. The anomaly is considered a degenerative eye disease and is erroneously confused with cataract. It displays similar features to those of tumors, such as local invasion, metaplasia of epithelial cells, presence of oncogenic viruses (human papilloma virus), inactivation of tumor suppressor genes (e.g., p53), and loss of heterozygosity. The treatment of pterygium is based on factors such as the evolution and progression of the disease, risk factors, symptoms, and patient age. Considerations about the best technique for the surgical removal of pterygium remain controversial, and complications and recurrence are very common. The development of new surgical techniques and adjuvant drugs is thus necessary. This study aims to analyze and compare the frequency of the GSTT1 genotypes in relation to pterygium through statistical analyzes in order to build a genotypic profile for the Replicon patients. The genotypic profile of the GSTT1-null polymorphism in Goiânia showed no significant difference when the frequency of the null genotype was compared between the control and experimental groups. The null genotype was more frequent in the population studied. Furthermore, the GSTT1 genotype was not related to the analyzed risk factors for pterygium, namely gender, ethnicity, family history, occupational exposure, smoking, hypertension, and diabetes.
Assuntos
Glutationa Transferase/genética , Polimorfismo Genético , Pterígio/genética , Brasil , Estudos de Casos e Controles , Diagnóstico Diferencial , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pterígio/etnologia , Fatores de RiscoRESUMO
Genetic polymorphisms are defined as changes within the DNA sequences of genes that have frequencies in the population higher than 1%. The glutathione S-transferases play an important role in the cellular detoxification systems involved in oxidative stress that can lead to accumulation of reactive oxygen species. Epidemiological studies have suggested that individuals with homozygous deletion of glutathione S-transferase mu 1 (GSTM1) and glutathione S-transferase theta 1 (GSTT1) are at higher risk of developing several types of neoplasias. The p53 protein is highly expressed in tumors and transformed cells, and the p53 is a classical tumor suppressor gene involved in regulating cell growth and development. In this study, we investigated the prevalence of polymorphisms in the p53, GSTM1, and GSTT1 genes in a population from Goiânia. We evaluated the polymorphisms of these genes in peripheral blood samples. The null or present polymorphism of GSTM1 and GSTT1 genes and Arg/Pro of the p53 gene were analyzed. Our results revealed a higher frequency of the GSTM1-null polymorphism (72.4%) than the GSTM1-present genotype (27.6%). For GSTT1, we observed higher frequency for the null genotype (65.5%) compared to the present genotype (34.5%). Analysis of p53 gene polymorphisms showed a higher frequency for the genotype Arg/Pro (66%) and a lower frequency for the Arg/Arg (23%) and Pro/Pro (11%) genotypes. It is essential to understand polymorphism frequencies in different populations and to evaluate the role of genetic polymorphisms and their effects on health.