rs1549758

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.

This case-control study investigated associations between five NOS3 gene polymorphisms and osteonecrosis of the femoral head (ONFH) in Korean patients with systemic lupus erythematosus. Two exonic NOS3 variants were significantly associated with ONFH risk: rs1549758 (Asp258Asp) and rs1799983 (Glu298Asp, G894T) showed OR 2.7-3.8 (p=1.0×10⁻⁵-5.0×10⁻⁴). The rs1799983-rs1800780 haplotype G-A was protective (OR 0.39, p=1.6×10⁻³), while haplotype T-A increased risk (OR 3.17-3.73, p=2.0×10⁻⁵-6.0×10⁻⁴).

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).