Relationships among N,N-dimethylformamide exposure, CYP2E1 and TM6SF2 genes, and non-alcoholic fatty liver disease

• Published in: Ecotoxicology and environmental safety Vol. 228; p. 112986
• Main Authors: Zhou, Ziqi, Sang, Lingli, Wang, Jin, Song, Lin, Zhu, Lejia, Wang, Yangmei, Xiao, Jing, Lian, Yulong
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 25.12.2021; Elsevier
• Subjects: CYP2E1; N, N-dimethylformamide; Non-alcoholic fatty liver disease; TM6SF2; CYP2E1; Non-alcoholic fatty liver disease; N, N-dimethylformamide; TM6SF2
• ISSN: 0147-6513; 1090-2414
• DOI: 10.1016/j.ecoenv.2021.112986

This study aimed to examine the relationships among N, N-dimethylformamide (DMF) exposure, cytochrome P4502E1 (CYP2E1) single nucleotide polymorphisms (SNPs) (rs2031920, rs3813867, rs6413432), transmembrane 6 superfamily member 2 (TM6SF2) SNP rs58542926 and non-alcoholic fatty liver disease (NAFLD). Baseline data were collected from participants who were then followed for 5 years in a prospective cohort study. The cohort initially consisted of 802 workers and ultimately included 660 people, all of whom underwent annual occupational health examinations from 2010 to 2015. The above-threshold group (≥7.3 mg/m³ adjusted relative risk (RR)= 3.620, 95%CI 2.072–6.325) was significantly more likely to develop NAFLD than the below-threshold group (<7.3 mg/m³). The TM6SF2 SNP rs58542926 CT (adjusted RR=3.921, 95% CI 2.329–6.600, P = 0.000) and CT+TT (adjusted RR=4.385, 95% CI 2.639–7.287, P = 0.000) genotypes were risk factors for NAFLD, as compared with the TM6SF2 rs58542926 CC genotype. Each dose group (below-threshold group and above-threshold group) interacting with the genotype of TM6SF2 SNP rs58542926 had an adjusted RR from 7.764 (95% CI 3.272–18.420, P = 0.000) to 24.022 (95% CI 8.971–64.328, P = 0.000). The T allele of rs58542926 in the TM6SF2 gene may be a risk factor for susceptibility to DMF-induced NAFLD. Polymorphisms of TM6SF2 SNP rs58542926 may play an important role in susceptibility to NAFLD after exposure to DMF. •The above-threshold group (≥7.3 mg/m³) was more likely to develop NAFLD.•The TM6SF2 SNP rs58542926 is a risk factor for NAFLD.•The T allele of TM6SF2 may be a risk factor for susceptibility to DMF-induced NAFLD.