性早熟女童雌激素受体α基因多态性与环境内分泌干扰物效应关系的研究  

Study on effect relationship between estrogen receptor α gene polymorphism and environmental endocrine disruptors in precocious girls

作　　者：柯江维[1] 杨玉[1] 段荣[1] 杨利[1] 刘志强[1] 颜兴伟 冯长华 

机构地区：[1]江西省儿童医院,江西南昌330006 [2]南昌市疾病控制中心

出　　处：《中国妇幼保健》2013年第25期4184-4187,共4页Maternal and Child Health Care of China

基　　金：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〕

摘　　要：目的:探讨性早熟女童雌激素受体α(ERα)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月至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4种(4-NP、P,P'-DDE、DBP、DEHP)环境内分泌干扰物(EEDs)的含量,同时测定子宫、卵巢体积、骨密度及血清雌二醇(E2)含量,将血清中4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雌激素受体α(ERα)基因多态性分析,观察他们之间的效应关系。结果:正常儿童38.4%血清中检测到P,P'-DDE,58.0%的血清中检测到4-NP,37.0%的血清中检测到DEHP,31.0%的血清中检测到DBP;性早熟患儿每例血清中均检测到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,且含量都高于正常儿童;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。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要严重得多,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基因多态性引起,其中Xx是EEDs的易感基因型。Objective： To explore the relationship between estrogen receptor α （ERα） gene polymorphism and environmental en- docrine disruptors in precocious girls, clarify the molecular mechanisms of difference of body; susceptibility to environmental endocrine dis- ruptors. Methods： One hundred and twenty - three precocious girls who were diagnosed definitely after first visit in endocrine department of the hospital from May 2011 to September 2012 were collected as study group, 102 normal girls during the same period were selected as con- trol group ; high performance liquid chromatography （HPLC） was used to detect the contents of four kinds of environmental endocrine disrup- tors （4 - NP, P, P＇ -DDE, DBP, DEHP） in study group and control group; in the meantime, uterine volume, ovarian volume, bone min- eral density （BMD）, and serum estradiol content were measured; the correlation between four kinds of environmental endocrine disruptors and clinical indexes of target organs was analyzed ; PCR - RFLP technique was used to analyze ERα gene polymorphisms in precocious girls with four kinds of environmental endocrine disruptors from study group and normal girls without four kinds of environmental endocrine disrup- tors from control group, the effect relationship was observed. Results： In control group, P, P＇ - DDE was detected in 38.4% of the girls, 4 - NP was detected in 58.0% of the girls, DEHP was detected in 37.0% of the girls, DBP was detected in 31.0% of the girls. In study group, P, P＇ - DDE was detected in all the girls, 4 - NP was detected in 89.7% of the girls, DEHP was detected in 63.3% of the girls, DBP was detected in 64. 8% of the girls, and the contents of four kinds of environmental endocrine disruptors in study group were higher than those in control group. In study group, serum 4 - NP content was positively correlated with uterine volume, ovarian volume and BMD ; there was a positive correlated between serum P, P＇ -DDE content and uterine volume; the odds ratio of Xx genotype

关 键 词：性早熟女童 雌激素受体α(ERα) 基因多态性 环境内分泌干扰物 

分 类 号：R585[医药卫生—内分泌]