Quantitative and causal analysis for inflammatory genes and the risk of Parkinson's disease.
Quantitative and causal analysis for inflammatory genes and the risk of Parkinson's disease.
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DOI：
10.3389/fimmu.2023.1119315
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发表时间：
2023
影响因子：
7.3
通讯作者：
Zhang, Yuan
中科院分区：
文献类型：
--
作者：
Yi, Minhan;Li, Jiaxin;Jian, Shijie;Li, Binbin;Huang, Zini;Shu, Li;Zhang, Yuan
帕金森病（Parkinson 'sdisease，PD）的发病机制与免疫系统功能紊乱和炎症反应有关。细胞因子、氧化应激、神经毒素和代谢相关酶参与了PD的神经炎症反应，参与这些反应的基因与PD的发病风险相关。在我们的研究中，我们对炎症基因和PD风险之间的关系进行了定量和因果分析。采用标准方法进行定量分析。主要结果分析采用等位基因模型（AM），次要结果分析采用显性模型（DM）和隐性模型（RM）。然后，对于那些与PD风险显著相关的基因，我们使用已发表的孟德尔随机化（MR）的GWAS汇总统计量来检验它们之间的因果分析。我们纳入了18个基因中的36个变体用于最终合并分析。结果表明，IL-6 rs 1800795、TNF-α rs 1799964、PON 1 rs 854560、CYP 2D 6 rs3892097、HLA-DRB rs660895、BST 1 rs 11931532、CCDC 62 rs 12817488多态性与PD的风险相关，OR值为0.66 ~ 3.19，而IL-1α、IL-1β、IL-10、MnSOD、NFE 2L 2、CYP 2 E1、NOS 1、NAT 2、ABCB 1、HFE和MTHFR与PD的危险性无关。此外，我们观察到增加ADP-核糖基环化酶（编码为BST 1）对PD风险的增加具有因果作用（OR[95%CI] =1.16[1.10-1.22]），而PON 1（编码为PON 1）对PD风险可能具有保护作用（OR[95%CI] =0.81[0.66-0.99]）。IL-6、TNF-α、PON 1、CYP 2D 6、HLA-DRB、BST 1、CCDC 62等炎症基因多态性与PD易感性相关，ADP-核糖基环化酶和PON 1与PD发病风险存在因果关系，这可能有助于了解PD发病机制和途径。
The dysfunction of immune system and inflammation contribute to the Parkinson’s disease (PD) pathogenesis. Cytokines, oxidative stress, neurotoxin and metabolism associated enzymes participate in neuroinflammation in PD and the genes involved in them have been reported to be associated with the risk of PD. In our study, we performed a quantitative and causal analysis of the relationship between inflammatory genes and PD risk. Standard process was performed for quantitative analysis. Allele model (AM) was used as primary outcome analysis and dominant model (DM) and recessive model (RM) were applied to do the secondary analysis. Then, for those genes significantly associated with the risk of PD, we used the published GWAS summary statistics for Mendelian Randomization (MR) to test the causal analysis between them. We included 36 variants in 18 genes for final pooled analysis. As a result, IL-6 rs1800795, TNF-α rs1799964, PON1 rs854560, CYP2D6 rs3892097, HLA-DRB rs660895, BST1 rs11931532, CCDC62 rs12817488 polymorphisms were associated with the risk of PD statistically with the ORs ranged from 0.66 to 3.19 while variants in IL-1α, IL-1β, IL-10, MnSOD, NFE2L2, CYP2E1, NOS1, NAT2, ABCB1, HFE and MTHFR were not related to the risk of PD. Besides, we observed that increasing ADP-ribosyl cyclase (coded by BST1) had causal effect on higher PD risk (OR[95%CI] =1.16[1.10-1.22]) while PON1(coded by PON1) shown probably protective effect on PD risk (OR[95%CI] =0.81[0.66-0.99]). Several polymorphisms from inflammatory genes of IL-6, TNF-α, PON1, CYP2D6, HLA-DRB, BST1, CCDC62 were statistically associated with the susceptibility of PD, and with evidence of causal relationships for ADP-ribosyl cyclase and PON1 on PD risk, which may help understand the mechanisms and pathways underlying PD pathogenesis.
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影响因子：
2.1
作者：
Bowden J;Davey Smith G;Haycock PC;Burgess S
通讯作者：
Burgess S
影响因子：
1.8
作者：
Akhmedova, S;Anisimov, S;Schwartz, E
通讯作者：
Schwartz, E
影响因子：
6
作者：
Borie, C;Gasparini, F;Grandchamp, B
通讯作者：
Grandchamp, B
影响因子：
2.5
作者：
Buchanan, DD;Silburn, PA;Mellick, GD
通讯作者：
Mellick, GD
影响因子：
4.2
作者：
Chang, Kuo-Hsuan;Wu, Yih-Ru;Chen, Chiung-Mei
通讯作者：
Chen, Chiung-Mei