Ephx1, also known as microsomal epoxide hydrolase 1, is an evolutionarily conserved biotransformation enzyme. It converts epoxides to diols and can either detoxify or bioactivate a wide range of substrates, playing a role in the metabolism of exogenous carcinogens such as cigarette-smoking products [5]. Mutations and polymorphic variants in the Ephx1 gene have been associated with susceptibility to several human diseases, suggesting its importance in disease-related biological processes [5].

Ephx1 polymorphisms are associated with various diseases. For instance, the Ephx1 rs1051740 polymorphism is significantly associated with a high risk of chronic obstructive pulmonary disease (COPD), especially the C allele in Asians and the CC genotype in Caucasians [1]. The rs2234922 polymorphism may be a protective factor against COPD in Asians [1]. In epilepsy, Ephx1 rs1051740 and rs2234922 polymorphisms affect carbamazepine metabolism [2]. In lung cancer, the low-activity genotype of Ephx1 polymorphism at exon 3 is associated with a decreased risk among whites [3]. The Tyr113His polymorphism of Ephx1 contributes to the risk of hepatocellular carcinoma, especially in Asians, Caucasians, HBV-or HCV-dominant areas, and high-or medium-rate areas of HCC [4]. The Tyr113His polymorphism may also be a risk factor for head and neck cancer [6].

In conclusion, Ephx1 is a crucial biotransformation enzyme with a significant impact on multiple disease conditions including COPD, epilepsy, various cancers. The study of Ephx1 polymorphisms through genetic models helps in understanding its role in disease susceptibility and drug metabolism, providing valuable insights for disease prevention and individualized treatment strategies.

References:

1. Yang, Qinjun, Huang, Wanqiu, Yin, Dandan, Tong, Jiabing, Li, Zegeng. 2023. EPHX1 and GSTP1 polymorphisms are associated with COPD risk: a systematic review and meta-analysis. In Frontiers in genetics, 14, 1128985. doi:10.3389/fgene.2023.1128985. https://pubmed.ncbi.nlm.nih.gov/37284064/

2. Zhao, Gui-Xin, Shen, Ming-Li, Zhang, Zheng, Xie, Chun-Xiang, He, Gong-Hao. 2019. Association between EPHX1 polymorphisms and carbamazepine metabolism in epilepsy: a meta-analysis. In International journal of clinical pharmacy, 41, 1414-1428. doi:10.1007/s11096-019-00919-y. https://pubmed.ncbi.nlm.nih.gov/31650507/

3. Kiyohara, Chikako, Yoshimasu, Kouichi, Takayama, Koichi, Nakanishi, Yoichi. . EPHX1 polymorphisms and the risk of lung cancer: a HuGE review. In Epidemiology (Cambridge, Mass.), 17, 89-99. doi:. https://pubmed.ncbi.nlm.nih.gov/16357600/

4. Wang, D, Zhai, J X, Zhang, L M, Liu, D W, Liu, X H. . [EPHX1 Tyr113His polymorphism contributes to hepatocellular carcinoma risk: evidfnce from a meta-analysis]. In Molekuliarnaia biologiia, 49, 351-61. doi:. https://pubmed.ncbi.nlm.nih.gov/26065263/

5. Václavíková, Radka, Hughes, David J, Souček, Pavel. 2015. Microsomal epoxide hydrolase 1 (EPHX1): Gene, structure, function, and role in human disease. In Gene, 571, 1-8. doi:10.1016/j.gene.2015.07.071. https://pubmed.ncbi.nlm.nih.gov/26216302/

6. Chen, Hong, Ge, Lin, Sui, Qiuli, Lin, Mei. 2015. Systematic Review and Meta-Analysis of the Relationship between EPHX1 Polymorphisms and the Risk of Head and Neck Cancer. In PloS one, 10, e0123347. doi:10.1371/journal.pone.0123347. https://pubmed.ncbi.nlm.nih.gov/25923690/