NOS1 SNPs rs1047735, rs2682826, and rs3741475 and NOS2A SNPs rs1060826, rs2297518, and rs3730013 genotyping was conducted at Stanford Human Genome Center; PCR (polymerase chain reaction) assays were conducted with TaqMan Universal Master Mix (Applied Biosystems), primers and probes were designed based on the NCBI (National Center for Biotechnology Information) DNA sequence and purchased from ABI (Applied Biosystems).
To safeguard against systematic genotype errors due to using different genotyping centers for fill-in genotyping of NOS1 SNPs rs1047735 and rs2682826, and NOS2A SNPs rs1060826, rs2297518, and rs3730013, 97 participants were included in both genotyping experiments; they provided an interlaboratory genotype call rate concordance of 99.
homozygous for the major allele) for NOS1 rs1047735 and rs2682826, to compare with prior report (Levecque et al.
Gene-environment interactions were assessed with NOS1 rs2682826 and pesticide use due to previous report (Hancock et al.
We did not find any other SNPs to be significantly associated with PD, aside from NOS1 rs1047735 based on an additive model without adjustment for PON1; however, we did not detect an association with the a priori selected dominant model (Levecque et al.
Investigating NOS1 rs2682826 and any household pesticide, we estimated a nonsignificant interaction based on the p-value of the product term (p = 0.
In secondary, exploratory analysis, we detected three other significant statistical interactions between NOS1 SNPs rs1047735, rs816353, and rs3741480, and ambient OP exposure (Table 3).
In our population, while controlling for PON1, OP exposure was positively associated with PD, and variation in multiple regions throughout the NOS1 gene further modified this association.
We also did not replicate previous positive marginal associations reported for NOS1 rs1047735 or rs2682826.