Polymorphisms of Cytochromes P450 and Glutathione S-Transferases Synergistically Modulate Risk for Parkinson’s Disease

• DOI: 10.3389/fnagi.2022.888942
• Publication Date: 2022-04-29T06:40:52Z
• Authors: Hui-Hui Fan; Bao-Qing Li; Ke-Yun Wu; Hai-Dan Yan; Meng-Jie Gu; Xing-Hao Yao; Hao-Jia Dong; Xiong Zhang; Jian-Hong Zhu
• Keywords: GSTP1; Glutathione S-transferase; Xenobiotic

Background Environmental substances such as pesticides are well-known in link with Parkinson’s disease (PD) risk. Enzymes including cytochromes P450 (CYPs), esterases and glutathione S-transferases (GSTs) responsible for the xenobiotic metabolism may functionally compensate each other subtypes same class. We hypothesize that genetic effects of class modulate PD risk stronger a synergistic way than individually. Methods selected 14 polymorphic loci out 13 genes which encode enzymes classes CYP, esterase, GST, recruited cohort 1,026 control subjects from eastern China. The genotypes were identified using improved multiplex ligation detection reaction analyzed multiple models. Results A total polymorphisms remained after Hardy-Weinberg equilibrium analysis. None independently associated Bonferroni correction either by logistic regression or In contrast, interaction analyses detected increased resistance to individuals carrying rs12441817/CC ( CYP1A1 ) rs2070676/GG + GC CYP2E1 P = 0.002, OR 0.393, 95% CI 0.216–0.715), GSTM1 -present, GSTT1 -null, rs156697/AG GG GSTO2 rs1695/AA GSTP1 0.003, 0.348, 0.171–0.706). effect GST s on was primarily present females 0.003). No observed within esterases. Conclusion demonstrate presence but not individual impact susceptibility CYPs GSTs . results indicate interplay leads development metabolizing enzymes.