特发性中枢性性早熟女童雌激素受体β基因Rsa Ⅰ和Alu Ⅰ多态性的研究

发布时间：2018-04-24 05:25

本文选题：特发性中枢性性早熟 + 雌激素受体β基因　；参考：《南方医科大学》2017年硕士论文

【摘要】：1.研究背景性早熟是指女童在8岁前、男童在9岁前出现第二性征的发育。根据发病机制可分为中枢性性早熟(central precocious puberty,CPP)、外周性性早熟(peripheral precocious puberty,PPP)及部分性早熟。中枢性性早熟中无器质性病变的则称之特发性中枢性性早熟(idiopathic central precocious puberty,ICPP),ICPP主要因下丘脑-垂体-性腺轴功能的提前释放(Hypothalamic-pituitary-gonad alaxis,HPGA)而使儿童出现乳腺发育、月经早潮、骨骺提前闭合,身材矮小等表现。随着生活水平的提高,饮食习惯和周围环境的改变,性早熟的发病率呈逐年上升的趋势[2],多见于女童。性早熟的病因和发病机制复杂多样,因器质性疾病导致性早熟较少,多数因内分泌功能紊乱引起[37]。最近研究指出环境内分泌干扰物(environmental endocrine disruptors,EEDs)能够通过影响 HPGA 的启动和功能,引起机体内分泌系统功能紊乱而导致性早熟。在基因突变和基因多态性研究的基础上探索性早熟的病因越来越受到关注。但雌激素受体β基因多态性与性早熟的相关报道较少[17-19]。本研究拟检测ICPP女童雌激素受体β基因Rsa Ⅰ、Alu Ⅰ基因多态性,探讨其与中枢性性早熟发生的关系。2.研究目的通过观察ICPP女童ERβ基因Rsa Ⅰ、Alu Ⅰ多态性,探讨与中枢性性早熟发生的关系,为其分子遗传基础提供依据。3材料与方法3.1研究对象从2013年1月到2014年08月在深圳市妇幼保健院儿科内分泌门诊及住院部的病人中选取100例ICPP女童。她们经体格检查、临床表现和影像学检查,再经过GnRH激发试验均符合ICPP的诊断标准[61-62]。所有的研究对象初次就诊的年龄在4-10.5岁,平均为(6.690±1.580)岁。在同一时期随机选择在我院体检均健康的100例女童作为对照组,她们均生长发育正常,无相关肿瘤及慢性消耗性疾病。其就诊年龄在3.83-10.00岁,平均为(5.81±1.12)岁,ICPP组与对照组间的年龄差异无统计学意义(t=0.87,P0.05)。3.2实验方法(1)收集ICPP女童和对照组女孩的外周静脉血3ml,以待检测ERβ Rsa Ⅰ、Alu Ⅰ基因多态性。(2)通过PCR-DNA测序的方法,对ICPP女童和正常健康组女童的ERβ RsaⅠ和Alu Ⅰ基因多态性的长度进行检测,进一步发现ERβ基因Rsa Ⅰ、Alu Ⅰ的基因型分布和R等位基因及A等位基因的基因频率。(3)采用SPSS 13.0软件进行统计学的数据分析,分别统计两组基因型频率和等位基因频率的分布情况,组间差异用X2检验,计算OR值和95%CI,以P0.05有统计学意义。4.结果4.1 Rsa Ⅰ基因多态性分析Rsa Ⅰ基因型及R等位基因频率在两组中的分布差异均有统计学意义(X2=5.960,P=0.045;X2=4.771,P=0.029),ICPP 组的 R等位基因频率是41.50%,高于对照组的30.00%,OR值是1.579(95%CI 1.047～2.382,P0.05),ICPP组和对照组在基因型分布上分别是Rr与rr基因型所占比例较高,均为51%和48%。4.2 Alu Ⅰ基因多态性分析AluⅠ基因型及A等位基因频率在两组中分布差异均无统计学意义(X2= 2.889,P=0.236;X2=2.749,P=0.097),A等位基因频率在ICPP组中是18.5%,在对照组中则为12.5%,OR值是1.589(95%CI 0.916～2.755,P0.05),基因型分布上ICPP组和对照组中均是aa基因型所占比例较高,各占66%和76%。4.3 Rsa Ⅰ和Alu Ⅰ基因多态性联合分析9种单体型分布经卡方检验在两组间差异有显著统计学意义(X2=15.821,P=0.045),其中ICPP组Rraa基因型构成比(39%)高于对照组构成比(31%),而rraa基因型构成比(20%)低于对照组(42%)。5结论ERβ基因RsaⅠ多态性与ICPP的发病可能有关,携带Rsa Ⅰ的R等位基因发生ICPP的相对风险是r基因的1.579倍(95%CI 1.047～2.382,P0.05)。R等位基因可能是ICPP女童遗传易感基因,Rr基因型易于患病,Rraa基因型有可能是ICPP的潜在危险因素。
[Abstract]:1. background precocious precocious puberty refers to the child's development of secondary sex before the age of 8. According to the pathogenesis, it can be divided into central precocious puberty (CPP), peripheral precocious puberty (peripheral, precocious puberty, PPP) and partial precocious puberty. The non organic lesions of central precocious puberty are called idiopathic Sexual central precocious puberty (idiopathic central precocious puberty, ICPP), ICPP mainly due to the premature release of the hypothalamus pituitary - gonadal axis (Hypothalamic-pituitary-gonad alaxis, HPGA), which makes the children develop mammary development, menstrual early tide, early closure of the epiphysis, short body and so on. With the improvement of living standard, eating habits and weeks The incidence of precocious puberty is increasing year by year in [2], which is often seen in girls. The etiology and pathogenesis of precocious puberty are complex and varied, because of organic diseases that lead to less precocious puberty, and most of the endocrine dysfunction caused by [37]. recently indicated that the environmental endocrine disruptors (EEDs) can be found. The cause of precocious puberty is caused by the disturbance of the function of HPGA and the dysfunction of the endocrine system in the body. On the basis of gene mutation and gene polymorphism, the etiology of precocious puberty is becoming more and more concerned. However, the correlation between estrogen receptor beta gene polymorphism and precocious puberty is less [17-19]. this study is to detect ICPP girls Estrogen receptor beta gene Rsa I, Alu I gene polymorphism, to explore the relationship with central precocious puberty,.2. research aims to explore the relationship between ICPP girl ER beta gene Rsa I and Alu I polymorphism, explore the relationship with central precocious precocious puberty, and provide the basis for the molecular genetic basis of.3 materials and methods 3.1 from January 2013 to In 08 months of 2014, 100 ICPP girls were selected in the pediatric endocrinology clinic and inpatient department of Shenzhen maternal and child health care hospital. They were examined by physical examination, clinical manifestation and imaging examination, and the GnRH tests were all consistent with the diagnostic standard of ICPP [61-62].. The age of the first diagnosis was 4-10.5 years, the average was (6.690 + 1.580). In the same period, 100 girls were randomly selected as the control group in the physical examination of our hospital. All of them had normal growth and development, without related tumors and chronic consumptive diseases. The age of their treatment was 3.83-10.00 years old, the average age was (5.81 + 1.12) years old. There was no statistical significance (t=0.87, P0.05).3.2 test method (1) between group ICPP and control group. The peripheral venous blood 3ml of ICPP girls and control girls was collected to detect the polymorphism of ER beta Rsa I and Alu I gene. (2) the length of ER beta Rsa I and Alu I gene polymorphisms in ICPP girls and normal health groups were detected by PCR-DNA sequencing, and ER beta gene Rsa I, genotype distribution and etc. The gene frequency of the allele and A allele. (3) the SPSS 13 software was used to analyze the statistical data, and the distribution of the genotype frequency and allele frequency of the two groups were statistically analyzed. The difference between groups was calculated by X2 test, and the OR value and 95%CI were calculated, and P0.05 had statistical significance of.4. knot fruit 4.1 Rsa I gene polymorphism analysis of Rsa I genotype and R. The distribution of allele frequencies in the two groups were statistically significant (X2=5.960, P=0.045; X2=4.771, P=0.029), and the R allele frequency in ICPP group was 41.50%, higher than that of the control group, and the OR value was 1.579 (95%CI 1.047 to 2.382, P0.05), and the proportion of Rr and RR genotypes in the ICPP and control groups was higher, respectively. 51% and 48%.4.2 Alu I gene polymorphism analysis of Alu I genotype and A allele frequency in the two groups were not statistically significant (X2= 2.889, P=0.236; X2=2.749, P=0.097), and A allele frequencies were 18.5% in ICPP group, 12.5% in the control group and 1.589 in the OR (95%CI 0.916 to 2.755). In the control group, the proportion of AA genotypes was higher, each of which accounted for 66% and 76%.4.3 Rsa I and Alu I gene polymorphism combined analysis of 9 types of haplotype distribution through chi square test had significant statistical significance (X2=15.821, P=0.045), of which the ICPP group Rraa genotype ratio (39%) was higher than that of the control group (31%), and the rraa genostructure was found. Compared with the control group (42%).5 conclusion, the Rsa I polymorphism of ER beta gene may be related to the pathogenesis of ICPP. The relative risk of ICPP is 1.579 times that of R gene (95%CI 1.047 ~ 2.382, P0.05).R allele is likely to be the genetic susceptibility gene of the ICPP girls. Potential risk factors for P.

【学位授予单位】：南方医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R725.8

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