RESUMO
BACKGROUND: Deficiency of plasma glutathione peroxidase (GPx-3) has been associated with platelet-dependent thrombosis. Single-nucleotide polymorphisms (SNPs) in the promoter region of GPX3 gene have been found associated with the risk for ischemic stroke in Caucasian populations. The aim of our present study was to evaluate the impact of genetic variations in the GPX3 gene and plasma GPx-3 antigen levels on ischemic stroke in young Asian Indians. METHODS: One hundred patients with ischemic stroke and 200 age- and sex-matched controls were studied. Genetic analysis for the study population was done by a combination of variant screening using single-stranded conformation polymorphism and final genotyping by polymerase chain reaction-restriction fragment length polymorphism and allele-specific polymerase chain reactions. Plasma GPx-3 antigen levels were evaluated using commercial kits. Data were analyzed using genetic analysis software and statistical tools. RESULTS: Significantly higher GPx-3 levels were observed in controls compared with patients (controls 26.37 ± 3.66 µg/mL and patients 22.83 ± 4.57 µg/mL, P < .001). Only the SNP -861A/T was found associated with stroke phenotype (P < .0001). The SNP -568T/C was observed to significantly influence plasma GPx-3 levels (P < .05). The haplotype carrying the risk "T" allele of SNP -861A/T was significantly over-represented in patients with stroke (P < .0001). CONCLUSIONS: The T allele of -861A/T is a risk allele for the ischemic stroke phenotype. The -861A/T and -568T/C SNPs may show a statistically significant association with both plasma GPx-3 antigen levels and the stroke phenotype in a larger sample size.
Assuntos
Povo Asiático/genética , Isquemia Encefálica/genética , Glutationa Peroxidase/genética , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/genética , Adulto , Alelos , Isquemia Encefálica/sangue , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Testes Genéticos/métodos , Genótipo , Glutationa Peroxidase/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Fatores de Risco , Acidente Vascular Cerebral/sangue , Adulto JovemRESUMO
INTRODUCTION: Nitric oxide levels and NOS3 gene variants play a pivotal role in the development of vascular diseases/stroke. We attempted to determine the role of NOS3 gene variants and plasma NO levels towards the development of ischemic stroke in young Asian-Indians. METHODS: One hundred ischemic stroke patients and 200 age and sex matched control study subjects were screened for NOS3 gene variants using SSCP [single stranded confirmation polymorphism] and PCR based techniques. Plasma NO metabolites [NOx] were evaluated for the investigated population. RESULTS: Significantly higher NOx levels were observed in controls [controls 56.63±25.92 µmol/L, patients 34.73±19.88 µmol/L, p<0.001]. The SNPs [single nucleotide polymorphisms] 894G/T, 1998C/G and 2479G/A were found associated with the disease phenotype with the most significant finding observed for 894G/T [χ(2)=36.68, p<0.001]. The SNPs 894G/T and 2479G/A were significantly associated with NOx levels [p=0.001]. The haplotypes TCA and TGA were overrepresented in the patient population [p<0.0001]. CONCLUSION: Two NOS3 SNP [894G/T and 2479G/A] variants and NOx levels are associated with ischemic stroke in young Asian Indians. These NOS3 SNPs might represent genetic risk factors for ischemic stroke in young Asian Indians. However these observations need to be confirmed by larger replicate/cross-sectional studies.
