亚甲基四氢叶酸还原酶基因多态性与长期接触有机磷农药相互作用对2型糖尿病的影响

目的通过对亚甲基四氢叶酸还原酶(MTHFR)基因多态性的检测分析,探讨其基因型及等位基因与长期接触有机磷农药相互作用对2型糖尿病(T2DM)发生的影响。方法选择209例T2DM(病例组)和216例非T2DM人群(对照组)为研究对象。采用荧光定量PCR技术,对MTHFR(rs1801133)基因位点进行基因分型,应用Logistic回归分析基因、长期接触有机磷农药与T2DM发生的关系,应用叉生分析和广义多因子降维法探讨基因与长期接触有机磷农药之间的交互作用对T2DM发生的影响。结果体质指数(BMI)≥24、居住地为农村、有长期接触有机磷农药、有糖尿病家族史为T2DM发病的危险因素。MTHFR基因型分布符合Hardy-Weinberg平衡(P>0.05),病例组和对照组的基因型分布频率差异无统计学意义。在显性模型下,调整协变量后,CT、TT基因型个体T2DM的发病风险是CC基因型的1.667倍(95%CI1.057~2.627,P=0.028),提示携带T等位基因者较未携带T等位基因者发生T2DM的风险增加。叉生分析显示,MTHFR(rs1801133)与长期接触有机磷农药在相乘模型上的交互作用有统计学意义,说明二者之间的相乘交互作用在T2DM的发病中可能起作用。广义多因子降维法分析表明,MTHFR(rs1801133)基因、有糖尿病家族史两个因素构成的交互作用模型为最优模型。结论 MTHFR(rs1801133)CT、TT基因型可能为T2DM发病的危险因素,该基因多态性与环境因素间的交互作用增加了T2DM发病的风险。

Effects of methylenetetrahydrofolate reductase gene polymorphism and long-term exposure to organophosphorus pesticides on type 2 diabetes mellitus

OBJECTIVE To investigate the effect of the interaction between methylenetetrahydrofolate reductase(MTHFR) genotype and allele and long-term exposure to organophosphorus pesticides on the development of type 2 diabetes mellitus(T2 DM). METHODS A total of 209 cases of T2 DM(case group) and 216 cases without T2 DM(control group) were selected as subjects. The polymorphism of MTHFR(rs1801133) was detected by TaqMan probe technique. The relationship between genes, long-term exposure to organophosphorus pesticides and T2 DM was analyzed by Logistic regression. The interaction between gene and long-term exposure to organophosphorus pesticides was discussed by crossover analysis and generalized multifactor dimensionality reduction. RESULTS BMI≥24, residence in countryside, long-term exposure to organophosphorus pesticides and family history of diabetes mellitus were risk factors for T2 DM. MTHFR genotype distribution conformed to Hardy-Weinberg equilibrium(P>0.05). There was no significant difference in genotype distribution frequency between case group and control group. The risk of T2 DM in individuals with CT and TT genotypes was 1.667 times higher than that of CC genotypes after adjusting the covariates at rs1801133 locus in the dominant model(95%CI 1.057-2.627,P=0.028). It suggested that the samples of allele T had a increased risk of T2 DM compared with those without allele T. The above models still had statistical significance(P<0.05) after adjusting the covariates. Forth, crossover analysis showed that the gene MTHFR(rs1801133) and long-term exposure to organophosphorus pesticides had multiplication interaction. The interaction between gene MTHFR(rs1801133) and long-term exposure to organophosphorus pesticides may play a role in the pathogenesis of T2 DM. Generalized multifactor dimensionality reduction(GMDR)analysis showed that the interaction model of MTHFR(rs1801133) gene and family history of diabetes mellitus was the best model. CONCLUSION MTHFR(rs1801133) gene CT and TT genotype may be risk factors for T2 DM. The interaction between genetic polymorphism and environmental factors increases the risk of T2 DM.