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

Abstract

Objective: 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). Methods: 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. Results: 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. Conclusion: Polymorphisms of TM6SF2 SNP rs58542926 may play an important role in susceptibility to NAFLD after exposure to DMF.

Keywords

• Non-alcoholic fatty liver disease
• CYP2E1
• TM6SF2
• N, N-dimethylformamide