Division of Toxicology and Environmental Health, College of Public Health, Nantong University, Nantong, Jiangsu, China.
Jiaxing Maternal and Child Health Hospital, Zhejiang, China.
Ecotoxicol Environ Saf. 2019 Apr 30;171:347-351. doi: 10.1016/j.ecoenv.2018.12.055. Epub 2019 Jan 4.
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.
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.
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.
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.
目前的研究表明,N,N-二甲基甲酰胺(DMF)暴露与肝损伤有关,但 PNPLA3、GCKR、COL13A1 和 TM6SF2 基因多态性是否与肝损伤有关仍存在争议。我们的目的是研究 DMF 暴露、PNPLA3 rs738409、GCKR rs780094、COL13A1 rs1227756、TM6SF2 rs58542926 与肝损伤之间的关系。
该队列包括在中国接触 DMF 阈限值(TLV)以上的 461 名工人和接触 DMF TLV 以下的 211 名工人,随访 5 年。通过泊松分析还研究了 DMF 测量剂量与肝损伤相对风险(RR)之间的关系。使用逻辑回归模型检验 DMF 测量剂量、基因座与肝损伤 RR 之间的关系。所有工人都在太仓 CDC 的认证体检中心进行了年度体检,包括肝功能血清转氨酶评估和腹部超声检查。使用基因组 DNA 提取试剂盒从外周血白细胞中提取基因组 DNA。
DMF 接触 TLV 以上组的肝损伤发生率明显高于 TLV 以下组。GCKR rs780094 与肝损伤有关。GCKR rs780094、DMF 暴露与肝损伤之间的相互作用无显著相关性。
我们的数据表明,在 DMF 暴露中,GCKR rs780094 可能导致肝损伤的风险增加。我们的结果表明,GCKR rs780094 是一个有用的遗传标记,可以帮助识别肝损伤。