rs2297518

Genetic polymorphisms in oxidative stress-related genes were associated with treatment outcomes in aggressive B-cell non-Hodgkin lymphoma. In discovery (n=337) and validation (n=572) cohorts, rare homozygotes for MPO rs2243828 (HR=1.87, P=0.013) and AKR1C3 rs10508293 (HR=2.09, P=0.0032) were associated with increased risk of progression, while NCF4 rs1883112 rare homozygotes showed protective effects against progression (HR=0.66, P=0.06 discovery; HR=0.66, P=0.05 validation). Meta-analysis confirmed NCF4 association with improved survival outcomes (HR=0.66, P<0.01).

A case-control association study in Chinese populations (579 septic patients) found that the NOS2 rs2297518 G>A non-synonymous polymorphism (S608L) in exon 16 was significantly associated with increased susceptibility to septic shock (OR=3.29, 95% CI=1.40-7.72, P=0.0047 in Liaoning; OR=3.49, 95% CI=1.57-7.79, P=0.0019 in Jiangsu). Functional assays showed the at-risk GA genotype had 1.38-fold higher NOS2 enzyme activity compared to GG genotype (P=0.32).

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).