血清叶酸与RAR - β、MGMT甲基化在宫颈上皮内瘤变中的交互效应  

Interaction between serum folic acid and methylation of RAR-βand MGMT in cervical intraepithelial neoplasia

作　　者：巩璐 王金桃 朱京京 郭翀宇 冉朝霞 王璐 宋丽 吕元婧 丁玲 GONG Lu;WANG Jin-tao;ZHU Jing-jing;GUO Chong-yu;RAN Zhao-xia;WANG Lu;SONG Li;LYu Yuan-jing;DING Ling(Department of Epidemiology School of Public Health,Shanxi Medical University,Taiyuan Shanxi 030001,China;不详)

机构地区：[1]山西医科大学公共卫生学院流行病学教研室,山西太原030001 [2]陕西能源职业技术学院

出　　处：《现代预防医学》2022年第6期1099-1103,1117,共6页Modern Preventive Medicine

基　　金：国家自然科学基金(81703313,81872705);国家卫生和计划生育委员会公益性行业科研专项(201402010)。

摘　　要：目的探讨血清叶酸与RAR-β、MGMT启动子区CpG岛甲基化在宫颈上皮内瘤变(CIN)中的交互效应。方法基于课题组建立于山西省(介休市和阳曲县)的已婚妇女人群队列,选取2014年6月-9月病理学确诊的CIN患者(CINⅠ147例、CINⅡ/Ⅲ134例)及正常宫颈妇女(156例)为研究对象。收集全部对象人口学特征及相关因素,采集空腹静脉非抗凝血与宫颈脱落细胞。采用化学发光免疫法检测血清叶酸浓度,甲基化特异性PCR法检测基因CpG岛甲基化状态,导流杂交法判定HPV感染状况。采用Kruskal-Wallis H检验、χ^(2)检验、趋势χ^(2)检验进行资料分析,非条件logistic回归模型和交互作用指标评价交互效应。结果血清叶酸在NC、CINⅠ和CINⅡ/Ⅲ组总体分布差异有统计学意义(P<0.001)。低血清叶酸(≤23.13 nmol/L)可增加CINⅠ和CINⅡ/Ⅲ的发生风险(OR=6.78,95%CI:3.75~12.26;OR=64.13,95%CI:18.34~224.20),且随病变进展,血清叶酸逐渐降低(χ^(2)趋势=92.69,P<0.001)。CIN组RAR-β、MGMT CpG岛甲基化率均高于NC组,且甲基化率随病变进展逐渐上升(χ^(2)趋势=20.19,P<0.001;χ^(2)趋势=15.35,P<0.001)。在各组中低血清叶酸与RAR-β、MGMT CpG岛高甲基化均呈正相加交互作用(CINⅠ:S=2.23,95%CI:1.63~8.08,S=1.21,95%CI:1.01~10.01;CINⅡ/Ⅲ:S=2.43,95%CI:1.72~6.80,S=2.83,95%CI:1.55~8.10),但未显示相乘交互作用(P>0.05)。结论低血清叶酸和RAR-β、MGMT CpG岛高甲基化均可增加CIN的风险,且可能存在相加交互作用。Objective To explore the interaction between serum folate and promoter regions CpG island methylation of RAR-βand MGMT in cervical intraepithelial neoplasia(CIN).Methods Based on cohort of married women established in Shanxi Province(Jiexiu city and Yangqu county),CIN patients(147 cases of CINⅠ,134 cases of CINⅡ/Ⅲ)and normal cervical women(156 cases)diagnosed pathologically from June to September 2014 were selected.The demographic characteristics and related factors of all participants were collected,and fasting venous non-anticoagulated blood and cervical exfoliated cells were collected.Serum folate concentration was detected by chemiluminescence immunoassay,methylation specific PCR was used to detect the methylation status of CpG island,and diversion hybridization was used to determine the status of HPV infection.Data were analyzed by Kruskal-Wallis H test,chi-square test and trend of chi-square test.The interaction was evaluated by unconditional logistic regression model and interaction index.Results The overall distribution of serum folate in NC,CINⅠand CINⅡ/Ⅲwas significantly different(P<0.001).Low serum folate(≤23.13nmol/L)increased the risk of CINⅠand CINⅡ/Ⅲ(OR=6.78,95%CI:3.75-12.26;OR=64.13,95%CI:18.34-224.20),and serum folate decreased gradually with the severity of cervical lesions(χ^(2)trend=92.69,P<0.001).The methylation rates of RAR-βand MGMT in CIN groups were higher than those in NC group,and the methylation rate of genes increased gradually with the severity of cervical lesions(χ^(2)trend=20.19,P<0.001;χ^(2)trend=15.35,P<0.001).In CIN groups,low serum folate and hypermethylation of RAR-βand MGMT showed positive interaction(CINⅠ:S=2.23,95%CI:1.63-8.08,S=1.21,95%CI:1.01-10.01;CINⅡ/Ⅲ:S=2.43,95%CI:1.72-6.80,S=2.83,95%CI:1.55-8.10),but there was no multiplicative interaction(P>0.05).Conclusion Low serum folate and CpG island hypermethylation of RAR-βand MGMT increase the risk of CIN,and there might be additive interaction.

关 键 词：血清叶酸 CPG岛甲基化 宫颈上皮内瘤变 

分 类 号：R737.33[医药卫生—肿瘤]