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.

Genetic association of NOS1 exon18, NOS1 exon29, ABCB1 1236C/T, and ABCB1 3435C/T polymorphisms with the risk of Parkinson's disease

“…In this meta-analysis, we enrolled 4 articles [ 1 , 3 , 23 , 44 ] including 789 cases and 1369 controls to investigate the role of NOS1 exon18 polymorphism in Parkinson's disease. The result was shown in Table 3 .…”

“…In this retrospective analysis, 5 studies [ 1 , 3 , 23 , 44 , 45 ] involving 1246 cases and 1606 controls were included to explore the link between NOS1 exon29 polymorphism and PD. As shown in Fig.…”

“…[ 47 , 48 ] Previous studies have explored the potential influences of NOS1 exon18, exon29, and ABCB1 3435C/T, 1236C/T SNP on the susceptibility to PD. [ 1 , 3 , 18 , 23 – 33 , 44 , 45 ] However, the small size and the minor statistical power of the individual case-control studies led to the lack in consistency of their results. Thus, we did this meta-analysis to study the association of these 4 polymorphisms with the risk of Parkinson's disease.…”

“…Till now, 4 studies have reported the relationship of NOS1 exon18 with Parkinson's disease. Among those studies, 4 studies [ 1 , 3 , 23 , 44 ] indicated that NOS1 exon18 polymorphism was not connected to the risk of Parkinson's disease. Our meta-analysis demonstrated that this polymorphism contributed to the disease susceptibility.…”

Role of ADH2 and ALDH2 gene polymorphisms in the development of Parkinson's disease in a Chinese population

“…Moreover, familial aggregation and co-aggregation of Parkinson's disease have indicated that genetic factors also play an important role in the development of Parkinson's disease. Previous studies have shown that genes encoding b-site APP cleaving enzyme 1, myeloid cells 2, cyclooxygenase-2, aldehyde dehydrogenase 2, neuronal nitric oxide synthase, and bone marrow stromal cell antigen 1, all contribute to the development of this disease (Dai et al, 2015;Goudarzian et al, 2015;Gupta et al, 2015;Wang et al, 2015a,b;Zhang et al, 2015).…”