Endothelial nitric oxide synthase gene variants contribute to oxidative stress in COPD

• Published in: Biochemical and biophysical research communications 2007-09, Vol.361 (1), p.182-188
• Main Authors: Arif, Ehtesham, Ahsan, Aarif, Vibhuti, Arpana, Rajput, Charu, Deepak, Desh, Athar, Mohammad, Singh, Bhawani, Pasha, M.A. Qadar
• Format: Article
• Language: English
• Subjects: Adult; Chronic obstructive pulmonary disease; eNOS; Female; Gene Frequency; Genetic Linkage; Genotype; Haplotypes; Humans; Male; Malonaldehyde; Nitric Oxide Synthase Type III - genetics; Nitrite; Oxidative Stress - genetics; Polymorphism, Genetic; Polymorphisms; Pulmonary Disease, Chronic Obstructive - diagnosis; Pulmonary Disease, Chronic Obstructive - genetics; Pulmonary Disease, Chronic Obstructive - metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2007.07.008

Nitric oxide (NO) plays critical role in endothelial dysfunction and oxidative stress in COPD, pointing to the significance of endothelial nitric oxide synthase gene ( eNOS) variants. We investigated the association of −786T/C, −922A/G, 4B/4A, and 894G/T polymorphisms of eNOS with the disease and its impact on nitrite and malonaldehyde levels in 190 COPD patients and 134 healthy controls, all smokers. The −786C, −922G and 4A alleles were significantly over-represented in patients ( p = 0.02, p = 0.02, and p = 0.03, respectively). The haplotypes, −786C:4A, 4A:894G, −786C:894G, and −786C:4A:894G were significantly over-represented in patients ( p < 0.0001, p = 0.02, p = 0.02, and p < 0.0001, respectively), whereas, haplotypes, −786T:4B, 4B:894G, −786T:894G, and −786T:4B:894G were significantly under-represented in the patients ( p < 0.0001). The patients had significantly increased levels of nitrite ( p = 0.003) and malonaldehyde ( p < 0.0001). Combination of genotypes containing −786C and 4A alleles were greater in patients ( p ⩽ 0.05), and these combinations associated with decreased FEV1 value and nitrite level ( p = 0.03 and p = 0.04, respectively) and with increased malonaldehyde levels ( p = 0.02). The eNOS −786C, −922G, and 4A alleles, these alleles associated haplotypes and genotype combinations were over-represented in patients. The variants and their combinations of four polymorphisms of eNOS contribute to disturbed pulmonary function and oxidative stress in COPD.