Relationship between N,N-dimethylformamide exposure, PNPLA3, GCKR, COL13A1 and TM6SF2 genes, and liver injury.

ABSTRACT

BACKGROUND: Current researches show that N,N-dimethylformamide (DMF) exposure is associated with liver injury, but it is debatable whether PNPLA3, GCKR, COL13A1 and TM6SF2 gene polymorphisms are associated with liver injury. Our objective was to examine the relationship among DMF exposure, PNPLA3 rs738409, GCKR rs780094, COL13A1 rs1227756, TM6SF2 rs58542926 and liver injury. METHODS: The cohort consisted of 461 workers exposed above the DMF threshold limit value (TLV) and 211 exposed below the DMF TLV in China, who were followed for 5 years. The relationship between the measured dose of DMF and the relative risk (RR) of liver injury was also investigated by Poisson analysis. Logistic regression models were used to examine the association between measured dose of DMF, gene locus, and RR for liver injury. All workers had a annual physical examinations were conducted at certified physical examination centers in Taicang CDC, including liver serum transaminase assessment and abdominal ultrasound. Genomic DNA was extracted from peripheral blood leukocytes using a genomic DNA extraction kit. RESULTS: The incidence of liver injury in the above DMF TLV group was significantly higher than in the below DMF TLV group. GCKR rs780094 was associated with liver injury. The interaction among the GCKR rs780094, DMF exposure and liver injury showed no significant association. CONCLUSIONS: Our data indicated that in DMF exposure, GCKR rs780094 may contribute to the risk of liver injury. Our results suggest that GCKR rs780094 is a useful genetic marker to help identify liver injury.