The NF-κB pathway is involved in the pathogenesis of neurological disorders that have inflammation as a hallmark, including Parkinson’s disease (PD). Our objective was to determine whether common functional variants in the NFKB1, NFKBIA and NFKBIZ genes were associated with the risk of PD. A total of 532 Spanish PD cases (61% male; 38% early-onset, ≤ 55 years) and 300 population controls (50% ≤55 years) were genotyped for the NFKB1 rs28362491 and rs7667496, NFKBIA rs696, and NFKBIZ rs1398608 polymorphisms. We compared allele and genotype frequencies between early and late-onset, male and female, and patient’s vs. controls. We found that the two NFKB1 alleles were significantly associated with PD in our population (p = 0.01; total patients vs. controls), without difference between Early and Late onset patients. The frequencies of the NFKB1 variants significantly differ between male and female patients. Compared to controls, male patients showed a significantly higher frequency of rs28362491 II (p = 0.02, OR = 1.52, 95%CI = 1.10–2.08) and rs28362491 C (p = 0.003, OR = 1.62, 95%CI = 1.18–2.22). The two NFKB1 variants were in strong linkage disequilibrium and the I-C haplotype was significantly associated with the risk of PD among male (p = 0.002). In conclusion, common variants in the NF-kB genes were associated with the risk of developing PD in our population, with significant differences between male and female. These results encourage further studies to determine the involvement of the NF-kB components in the pathogenesis of Parkinson´s disease.

NF-κB 通路参与以炎症为标志的神经系统疾病的发病机制，包括帕金森病 (PD)。我们的目的是确定NFKB1、NFKBIA和NFKBIZ基因的常见功能变异是否与 PD 风险相关。对总共 532 例西班牙 PD 病例（61% 男性；38% 早发，≤ 55 岁）和 300 例人群对照（50% ≤ 55 岁）进行了 NFKB1 rs28362491和 rs7667496、NFKBIA rs696 和NFKBIZ rs1398608 多态性基因分型。我们比较了早发型和晚发型、男性和女性以及患者与对照之间的等位基因和基因型频率。我们发现，两个NFKB1等位基因与我们人群中的 PD 显着相关（p  = 0.01；患者总数与对照组），早发和晚发患者之间没有差异。男性和女性患者之间NFKB1变异的频率存在显着差异。与对照组相比，男性患者的 rs28362491 II ( p  = 0.02，OR = 1.52，95%CI = 1.10–2.08) 和 rs28362491 C ( p  = 0.003，OR = 1.62，95%CI = 1.18–2.22 )频率显着更高）。两个NFKB1变异体处于强连锁不平衡状态，IC 单倍型与男性 PD 风险显着相关（p  = 0.002）。总之，NF-kB 基因的常见变异与我们人群中患 PD 的风险相关，男性和女性之间存在显着差异。这些结果鼓励进一步研究以确定 NF-kB 成分在帕金森病发病机制中的参与。