低浓度芳香烃溶剂暴露对自然流产影响的基因多态性研究

Gene Polymorphism to the Effects of Low Level Aromatic Solvents Exposure on Spontaneous Abortion

目的 探讨女工芳香烃溶剂暴露和细胞色素P450氧化酶MSP1基因和谷胱甘肽S转移酶GSTM1基因的多态性对自然流产的影响。方法 采用回顾性流行病学调查方法,使用统一调查表,由经过培训的调查员在北京燕山地区调查了276个女工,其中有自然流产史者58人,无自然流产史者218人。结果 单因素分析发现:GSTM1缺失基因型可致女工自然流产的危险度显著增加[OR=2.07(95％,CI:1.15-3.71)],但未观察到MSPI基因及芳香烃溶剂暴露对女工自然流产的影响。采用多元Logistie回归模型,经文化程度、年龄、倒班、体重指数、被动吸烟、职业紧张混杂因素调整后,可见GSTM1缺失基因型能显著致女工自然流产危险度增加[OR=2.15(95％,CI:1.17～3.98)]。以GSTM1存在基因型和MSP1野生基因型为参照组,采用多元Logistie回归模型,并将文化程度、年龄、倒班、体重指数、被动吸烟、职业紧张混杂因素放入回归模型进行调整,在调整混杂因素前后,与参照组比较,均可见MSP1杂合子/突变基因型合并GSTM1缺失基因型使女工自然流产的危险性增加[OR=2.98(95％CI:1.17～7.59)]。结论 GSTM1缺失基因型的女工自然流产的危险度显著增加,GSTM1缺失基因型与MSP1突变纯合子/杂合子基因型之间对自然流产的影响存在相加的联合作用。

Objective To investigate the association between genetic polymorphisms of cytochrome P450 MSP1 gene and the glutathione s-transferase GSTM1 gene in female workers exposed to aromatic solvents and spontaneous abortion. Methods A retrospective epidemiological investigation was carried out among 276 female workers including 58 female workers with history of spontaneous abortion and 218 female workers without spontaneous abortion selected in Yanshan of Beijing by the trained investigators using the unified questionnaire. Results The spontaneous abortion of female workers was significantly associated with GSTM1 (absent) (OR=2.07, 95% CI: 1.15-3.71), but not MSP1 (present) and exposure to aromatic solvent. After adust-ment for major confounders including education, age, shift work, body mass index, passive smoking and occupational stress, the multiple logistic regression analysis showed that GSTM1 gene (absent) significantly increased the risk of spontaneous abortion of female workers (OR=2.15, 95% CI: 1.17-3.98). Before and after adjustment for major confounders including education, age, shift work, body mass index, passive smoking and occupational stess, the multiple regression analysis showed that GSTM1 (absent) combined with MSP1 (heterozygous variant type / homozygous variant type) significantly increased the risk of spontaneous abortion (OR=2.98, 95% CI:l. 17-7.59), using the group with GSTM1 (present) and MSP1 (homozygous wild type) as reference group. Conclusion Our data suggested a genetic influence on spontaneous abortion in this population, GSTM1 (absent) was significantly associaled with spontaneous abortion, also provide evidence of additional joint action of gene MSP1 (heterozygous variant type and homozygous variant type) and GSTM1 (absent) to spontaneous abortion.