title: An exonic G894T variant of endothelial nitric oxide synthase gene as a risk factor for ischemic stroke in North Indians.
abstract: Nitric oxide (NO) synthesized by endothelial nitric oxide synthase (eNOS) enzyme is a critical regulator of cerebrovascular homeostasis. Genetic variability of G894T and intronic 4ab polymorphism in eNOS could affect the expression and activity of eNOS enzyme, modulating NO levels in endothelium. This results in endothelial dysfunction, which can contribute to the pathogenesis of ischemic stroke. The purpose of the study was to evaluate the association of eNOS genetic polymorphisms (G894T and 4ab) with the occurrence of ischemic stroke through various genetic models. Both polymorphisms were genotyped in 120 ischemic stroke patients diagnosed with MRI and other ancillary techniques and 101 control subjects free of neurological abnormalities, using PCR-RFLP technique and direct PCR respectively. The genotypes of both G894T and 4ab variants were found to be in Hardy Weinberg equilibrium for cases and controls. The significant variation was observed in the genotypic and allelic frequencies for G894T polymorphism between cases and controls, indicating the association of G894T variability with ischemic stroke. However, the difference between cases and controls was insignificant for eNOS 4ab polymorphism with regard to genotypic and allelic distribution. Except for recessive model, both dominant (GT/TT vs. GG) and co-dominant (TT vs. GT or GT vs. GG) models indicated nearly two-fold and 1.93 increased risk of ischemic stroke for G894T polymorphism, but none of them suggested the influence of eNOS 4ab polymorphism on ischemic stroke susceptibility. Haplotype analysis revealed the higher frequency of GT-4bb genotype combination in cases as compared to controls, but without significant difference. The study concluded that SNP G894T variant is associated with ischemic stroke and might contribute to ischemic stroke susceptibility in North Indians. However, this outcome needs to be confirmed by studies with large sample size.
authors.affiliation: Department of Human Genetics, Guru Nanak Dev University Amritsar, Punjab, India.
authors.forename: Kirandeep
authors.initials: K
authors.lastname: Kaur
authors.affiliation: Uppal Neuro Hospital Amritsar, Punjab, India.
authors.forename: Ashok
authors.initials: A
authors.lastname: Uppal
authors.affiliation: Department of Human Genetics, Guru Nanak Dev University Amritsar, Punjab, India; nupamkaur@yahoo.com.
authors.forename: Anupam
authors.initials: A
authors.lastname: Kaur
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D005091:Exons; D005260:Female; D005787:Gene Frequency / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000235:genetics*
chemical_list: C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III