中国儿童保健杂志 ›› 2014, Vol. 22 ›› Issue (2): 138-141.

• 科研论著 • 上一篇    下一篇

性早熟女童雌激素受体基因多态性与环境内分泌干扰物效应关系的研究

柯江维1, 杨玉1, 段荣1, 杨利1, 刘志强1, 颜兴伟2, 冯长华2   

  1. 1 江西省儿童医院, 江西 南昌 330006;
    2 南昌市疾病控制中心, 江西 南昌 330006
  • 收稿日期:2013-06-28 发布日期:2014-02-10 出版日期:2014-02-10
  • 作者简介:柯江维(1972-)男, 江西人, 副主任技师, 硕士研究生, 主要研究方向为雌激素受体与内分泌免疫代谢病的关系。
  • 基金资助:
    江西省科技厅支撑计划项目(20111BBG70018-2);江西省卫生厅科技计划项目(20121119)

Study on relationship between estrogen receptor gene polymorphism of precocious girls and environmental endocrine disruptors.

KE Jiang-wei1, YANG Yu1, DUAN Rong1, YANG Li1, LIU Zhi-qiang1, YAN Xing-wei2, FENG Chang-hua2.   

  1. (1 Jiangxi Province Children's Hospital, Nanchang, Jiangxi 330006, China; 2 Centers for Disease Control of Nanchang, Nanchang, Jiangxi 330006, China)
  • Received:2013-06-28 Online:2014-02-10 Published:2014-02-10

摘要: 目的 研究性早熟女童雌激素受体α(estrogen receptor α, ERα)及雌激素受体β(estrogen receptor β, ERβ)基因多态性与环境内分泌干扰物效应的关系, 阐明机体对环境内分泌干扰物易感性差异的分子机制。方法 收集2011年5月-2012年9月在江西省儿童医院内分泌专科门诊就诊的初诊性早熟女童123例, 正常女童102例, 运用高效液相色谱法测定患儿和正常女童血清四种[4-壬基酚(4-NP)、1, 1-二氯-2, 2-双对氯苯乙烯(P, P-DDE)、邻苯二甲酸二丁酯(DBP)、邻苯二甲酸-2-乙基乙酯(DEHP)]环境内分泌干扰物(EEDs)的含量, 同时测定子宫、卵巢体积、骨密度及血清中雌二醇含量, 将血清中四种EEDs的含量与靶器官的临床指标做相关分析;进一步用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析技术, 对性早熟女童血清中分别能检出4-NP、DEHP、DBP 和P, P'-DDE 的患儿和正常对照分别不能检出以上4种内环境干扰物的女童ERα和ERβ基因多态性分析, 观察它们之间的效应关系。结果 正常儿童, 38.4%血清中检测到P, P'-DDE, 58%的血清中检测到4-NP, 37%的血清中检测到DEHP, 31%的血清中检测到DBP;性早熟患儿100%血清中均检测到P, P'-DDE, 89.7%的血清中检测到4-NP, 63.3%的血清中检测到DEHP, 64.8%的血清中检测到DBP, 且含量均高于正常儿童;性早熟女童血清中4-NP与子宫体积、卵巢容积、骨密度均呈正相关;P, P'-DDE与子宫体积也成正相关;ERα基因XbaⅠ基因型Xx以及ERβ基因RsaⅠ基因型RR在各组的危险度(OR)最高, Xx 与xx相比较, 分别对4-NP、DEHP、DBP和P, P'-DDE的易感性是2.52、7.01、6.21和2.63倍, RR与rr相比较, 分别对4-NP、DEHP、DBP 和P, P′-DDE的易感性是7.36、9.61、8.67和6.77倍。结论 性早熟女童所受4-NP、DEHP、DBP 和P, P'-DDE污染的程度比正常对照组女童严重, 而且不同种类的EEDs对靶器官的致病作用不同;暴露于EEDs的儿童并非都发生性早熟的原因之一可能是由ERα和ERβ基因多态性引起, 其中Xx和RR是EEDs的易感基因型。

关键词: 性早熟女童, 雌激素受体α, 雌激素受体β, 基因多态性, 环境内分泌干扰物

Abstract: Objective To study the relationship between estrogen receptor gene polymorphism of precocious girls and environmental endocrine disruptors, as well as, to clarify the molecular mechanisms of body's susceptibility to environmental endocrine disruptors differences. Methods The blood samples were collected from 123 cases of precocious girls and 102 cases of normal girls.The concentrations of 4-nonylphend (4-NP), dibutyl phthalate (DBP), DEHP and P, P-DDE in serum samples were measured by using high performance liquid chromatography(HPLC), the volume of the uterus and ovary, the bone density, the content of estradiol(E2) were determined at the same time.The contents of 4-NP, DBP, DEHP and P, P-DDE in serum of precocious girls and the indices of the target organs were analyzed by using correlation.Further, estrogen receptor α (ERα ) and estrogen receptor β (ERβ) gene polymorphisms were analyzed by using PCR-RFLP between the precocious girls who can be detected 4-NP, DEHP, DBP and P, P'-DDE in serum and normal controls who can not be detected the above four kinds of EEDs respectively and the effect relationship between them were observed. Results In normal control group, 4-NP, DEHP, DBP and P, P'-DDE, were detected in blood serum for 58%, 37%, 31% and 38.4% respectively, whereas, in precocious girls group, the four kinds of EEDs respectively were detected in blood serum for 89.7%, 63.3%, 64.8% and 100%.The levels of 4-NP, DEHP, DBP and P, P'-DDE in serum in precocious girl group were notably increased than those in control group(P all<0.01).In precocious girls group, there was a positive correlations between the 4-NP in volume of uterus and the volume of ovary and the density of bone;P, P'-DDE and volume of uterus also showed a the positive correlation.Compared girls with precocious puberty who can be detected 4-NP, DEHP, DBP and P, P'-DDE in serum and normal controls who can not be detected the above four kinds of EEDs respectively, there were significant differences in genotype distribution for the XbaⅠand the RsaⅠ polymorphism.Compared Xx with wild-type xx, the susceptibility to 4-NP, DEHP, DBP and P, P'-DDE was respectively 2.52, 7.01, 6.21 and 2.63 fold.Compared RR with wild-type rr, the susceptibility to 4-NP, DEHP, DBP and P, P'-DDE was respectively 7.36, 9.61, 8.67 and 6.77 fold. Conclusion Precocious girls are contaminated more severely than normal girls.Different kinds of EEDs might have different influencing extents to the target organs.Children exposed to EEDs haven't necessarily occurred precocious.One reason may be different genotypes expressed in different individuals.Xx and RR are susceptible genotypes to EEDs.

Key words: precocious girls, estrogen receptor α, estrogen receptor β, gene polymorphism, environmental endocrine disruptors

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