rs1137933

Genetic association study of nitric oxide synthase genes (NOS1, NOS2, NOS3) in neural tube defects (NTDs) in 3109 Caucasian samples from 745 families. The most significant association was rs4795067 (NOS2, AG genotype) with cranial NTDs (genoPDT p=0.0014), and a significant interaction between rs9658490 (NOS1, G allele) and MTHFR C677T polymorphism with anencephaly/acrania (p=0.0014). Results implicate all three NOS genes in NTD risk both independently and through interactions with MTHFR.

A case-control association study in African-Americans (279 cases, 166 controls) and Caucasians (198 cases, 123 controls) examined 39 SNPs in the NOS2A gene for pulmonary tuberculosis susceptibility. Ten NOS2A SNPs were associated with TB in African-Americans, with the strongest associations at rs2274894 (OR=1.84, 95% CI 1.23-2.77, p=0.003) and rs7215373 (OR=1.67, 95% CI 1.17-2.37, p=0.004). Strong gene-gene interactions were observed between NOS2A SNPs and variants in IFNGR1 and TLR4 genes, suggesting synergistic effects on TB susceptibility.

This case-control association study examined 336 Crohn's disease patients, 355 ulcerative colitis patients, and 536 healthy controls from Spain to test whether polymorphisms in the NOS2A (inducible nitric oxide synthase) gene influence inflammatory bowel disease susceptibility. The (CCTTT)n microsatellite allele 13 was associated with increased UC risk (OR=1.64, p=0.001), promoter SNPs rs2779251 and rs2779248 were associated with UC predisposition, and the haplotype C(-)GCC carrying both exonic risk alleles increased CD susceptibility (OR=1.74, p=0.007), suggesting NOS2A involvement in IBD etiology.

This family-based case-control study examined 50 SNPs across three nitric oxide synthase genes (NOS1, NOS2A, NOS3) in 1,065 Parkinson disease cases and 1,180 controls from 695 families. Significant associations with PD were found for 8 NOS1 SNPs (rs3782218, rs11068447, rs7295972, rs2293052, rs12829185, rs1047735, rs3741475, rs2682826; p=0.00083-0.046) and 7 NOS2A SNPs (rs2072324, rs944725, rs12944039, rs2248814, rs2297516, rs1060826, rs2255929; p=0.0000040-0.047) in early-onset sporadic PD families. Gene-environment interactions were detected between NOS1 SNPs (rs12829185, rs1047735, rs2682826) and pesticide exposure (p=0.012-0.034) and between NOS2A SNPs (rs2248814, rs1060826) and cigarette smoking (p=0.013-0.021).