title: Association of Polymorphism of Neuronal Nitric Oxide Synthase Gene with Risk to Parkinson's Disease.
abstract: Environmental factors are implicated in aging as well as genetic predisposition-induced Parkinson's disease (PD) pathogenesis. Wrongdoers increase oxidative stress and nitrosative burden, which eventually degenerate the nigrostriatal dopaminergic neurons. Inhibition of the expression of nitric oxide synthase (NOS), an enzyme responsible for nitric oxide (NO) biosynthesis, prevents the demise of the nigrostriatal dopaminergic neurons. Polymorphism of NOS is thus expected to alter PD susceptibility. The study therefore aimed to examine an association of neuronal NOS (nNOS) gene polymorphism with nitrite, an indicator of nitrosative load; lipid peroxidation, an index of oxidative stress and PD susceptibility. An age-matched case-control study was performed in the north Indian residents enrolled at the Neurology Department of the King George's Medical University, Lucknow, India. While nNOS exon 29 TT variant genotype [odds ratio (OR) = 2.20, 95 % CI = 1.08-5.34, P = 0.040], combined TT and CT variants [OR = 1.68, 95 % CI = 1.05-2.69, P = 0.031] and T allele [OR = 1.58, 95 % CI = 1.10-2.28, P = 0.014] were found to be significantly associated with PD susceptibility, no association between nNOS exon 18 [OR for TT carriers = 1.97, 95 % CI = 0.89-4.20, P = 0.09 and OR for T allele = 1.35, 95 % CI = 0.94-1.93, P = 0.098] and PD risk was observed. Lipid peroxidation was augmented in all patients irrespective of their genotype. While genotype independent increase in nitrite content was observed in PD patients of exon 29 polymorphic groups, only heterozygous variant genotype of exon 18 was associated with augmentation in nitrite level as compared with respective control. The results obtained thus demonstrate that selected nNOS polymorphisms do not significantly contribute to PD risk in north Indian population.
authors.affiliation: CSIR-Indian Institute of Toxicology Research, Post Box No. 80, Mahatma Gandhi Marg, Lucknow, 226 001, Uttar Pradesh, India.
authors.forename: Satya Prakash
authors.initials: SP
authors.lastname: Gupta
authors.affiliation: CSIR-Indian Institute of Toxicology Research, Post Box No. 80, Mahatma Gandhi Marg, Lucknow, 226 001, Uttar Pradesh, India.
authors.forename: Ritul
authors.initials: R
authors.lastname: Kamal
authors.affiliation: Department of Biotechnology, Deen Dayal Upadhyay Gorakhpur University, Gorakhpur, 273 009, Uttar Pradesh, India.
authors.forename: Sarad Kumar
authors.initials: SK
authors.lastname: Mishra
authors.affiliation: Department of Neurology, King George's Medical University, Lucknow, 226 003, Uttar Pradesh, India.
authors.forename: Maneesh Kumar
authors.initials: MK
authors.lastname: Singh
authors.affiliation: Department of Neurology, King George's Medical University, Lucknow, 226 003, Uttar Pradesh, India.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Shukla
authors.affiliation: CSIR-Indian Institute of Toxicology Research, Post Box No. 80, Mahatma Gandhi Marg, Lucknow, 226 001, Uttar Pradesh, India. singhmahendrapratap@rediffmail.com.
authors.forename: Mahendra Pratap
authors.initials: MP
authors.lastname: Singh
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015227:Lipid Peroxidation / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000235:genetics*; D009573:Nitrites / Q000378:metabolism; D016017:Odds Ratio; D010300:Parkinson Disease / Q000201:enzymology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D009573:Nitrites; C496320:NOS1 protein, human; D052248:Nitric Oxide Synthase Type I
keywords: Lipid peroxidation; Neuronal nitric oxide synthase; Nitrite; Parkinson’s disease; Polymorphism