{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T10:54:13Z","timestamp":1784199253281,"version":"3.55.0"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,3]]},"abstract":"\n Objective<\/jats:title>\n \n The pathogenic mechanisms of antituberculosis drug-induced liver injury (AT-DILI) remain unclear. Isoniazid and rifampicin may lead to hepatic accumulation of protoporphyrin IX in which heme synthesis ferrochelatase (FECH), a key rate-limiting enzyme, potentially plays an important role. This study aimed to investigate the combined effects of\n FECH<\/jats:italic>\n gene polymorphisms and promoter methylation on AT-DILI risk in the Eastern Chinese population.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n A 1\u2005:\u20051 matched case-control study was conducted, detecting one CpG island in the\n FECH<\/jats:italic>\n promoter and four single-nucleotide polymorphisms (SNPs). A multivariate conditional logistic regression was used to estimate the association between genotypes and the risk of AT-DILI by the odds ratios (OR) with 95% confidence intervals (CIs). Additive and multiplicative interactions between methylation status and SNPs were further analyzed: additive interactions via the relative excess risk due to interaction (RERI) with 95% CIs, and multiplicative interactions by incorporating methylation-SNP product terms into regression models.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Overall, 182 cases and 182 controls were included. Neither\n FECH<\/jats:italic>\n promoter methylation (adjusted OR: 0.978, 95% CI: 0.408\u20131.560,\n P<\/jats:italic>\n \u2005=\u20050.509) nor the four SNPs showed individual associations with AT-DILI risk (\n P<\/jats:italic>\n \u2005>\u20050.05). Crossover analyses revealed no significant genotype\u2013methylation interactions (\n P<\/jats:italic>\n \u2005>\u20050.05). Both additive (rs17063905 RERI: \u20100.556,\n P<\/jats:italic>\n \u2005=\u20050.691) and multiplicative interaction models (rs17063905, OR: 0.723,\n P<\/jats:italic>\n \u2005=\u20050.615) demonstrated no synergistic effects between methylation and polymorphisms.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n This research finds no significant association between\n FECH<\/jats:italic>\n promoter methylation status in the CpG island, polymorphisms, or their interactions and the risk of AT-DILI.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1097\/fpc.0000000000000583","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T01:00:07Z","timestamp":1763341207000},"page":"71-79","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":1,"title":["No interaction between genetic variants and DNA methylation of the ferrochelatase gene in relation to antituberculosis drug-induced liver injury"],"prefix":"10.1097","volume":"36","author":[{"given":"Fei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, The Jurong Hospital Affiliated to Jiangsu University, Jurong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingru","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, 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