rs2248814

This case-control genetic association study investigated two iNOS gene variants (rs2779249 and rs2248814) in 145 Achilles tendon pathology patients and 132 healthy controls. The rs2779249 CA genotype was significantly protective against Achilles tendinopathy (p=0.009; OR=0.46), showing a heterozygous advantage effect and remaining significant in males (p=0.016; OR=0.37) but not females. The rs2248814 variant showed no association with Achilles tendon pathology. Findings support a genetic contribution to Achilles tendon injury risk mediated through nitric oxide synthesis.

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 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).