Study On The Polymorphisms Of Estrogen Receptor Beta Gene Rsa ? And Alu ? In Girls With Idiopathic Central Precocious Puberty

1.Reserach backgroundPrecocious puberty is defined as onset of development of secondary sexual characteristics before 8 years old in girls and 9 in boys,which isa diseaseof abnormal growth and development.According to the pathogenesis,precocious puberty is divided into three major forms,including central precocious puberty,peripheral precocious puberty and partial precocious puberty.Central precocious puberty which has no organic lesions is called idiopathic central precocious puberty(ICPP).ICPP mainly manifestes as breast development,early menstruation,epiphyseal closure,and microsomia,which is resulted from hypersecretion of gonadotropin-releasing hormoneand promotion of the function of hypothalamic-pituitary-gonadal axis ahead of schedule.With the adjustment of living style,diet custom and the surrounding environment,the morbidity of ICPP has gradually risen in recent years[2],The etiology of precocious puberty is complicated,less caused by organic disease,most caused by endocrine disorders[37].Recent studies have shown that EEDscan affect the starting and function of hypothalamus-pituitary-gonadal,lead to the organismic endocrine disorders.Thus,EEDs play an vital role in the occurrence and development of precocious puberty.With the in-depth study of gene mutation and gene polymorphism,the etiology of precocious puberty at the genetic level becomes more and more concerned.However,there are few reports on the reletionship between estrogen receptor gene polymorphism and precocious puberty.This study is designed to detect the estrogen receptor beta gene Rsa ??Alu ? polymorphisms of girls with ICPP,and investigate the correlation between estrogen receptor ?gene polymorphism and ICPP.2.ObjectiveThis study is designed to detect the estrogen receptor beta gene Rsa ??Alu ?polymorphisms of girls with ICPP,and discuss the relationship between estrogen receptor ?gene polymorphisms and ICPP,and provide the basis for the molecular genetics.3.Materials and Methods3.1 Meterials100 girls with ICPP were chosen as the case group,diagnosed by clinical symptoms,the medical image and hormone detection in pediatric endocrine outpatient and inpatient of Shenzhen Maternal and Child Health Care Hospital between January 2013 and August 2014.The age of newly diagnosed 4-10.5 years old(average 6.690±1.580).All of the children were consistent with the diagnostic criteria of precocious puberty after a detailed history and physical examination,and gonadotropin-releasing hormone(GnRH)stimulation test[2-3].Meanwhile,100 health girls,aged 3.83 to 10.00 years old(mean 5.81 ±1.12),who did not appear secondary sex characteristic and chronic wasting disease,belonged to the control group by random selection in our hospital.There was no statistical significance(t = 0.87,P>0.87)between the case and control group.3.2 Methods(1)In idiopathic central precocious puberty and normal healthy children,cubital vein 3ml of blood was kept using EDTA anticoagulant,to be used for detectingRsa? and Alu? genetic polymorphism.(2)Rsa? and Alu? gene polymorphisms were detected by polymerase chain reaction(PCR)in 100 ICPP and healthy girls.The distribution of genotypes of ER?gene Rsa? and Alu? and alleles frequency of R and X genes were statistically analyzed between the case and control group.(3)SPSS 13.0 software was applied for statistical analysis.The frequencies distribution of genotypes and allele were analyzed between the case group and control group.The difference was calculated by chi-square testbetween the two groups.The OR and 95%CI showed the correlocation strength,P<0.05 was statistically significant.4.Results4.1 Rsa? restriction site polymorphism analysis Frequency distribution of RasI genotype and R allele showed significant difference between the two groups(X2=5.960,P=0.045;X2=4.771,P=0.029).R allele frequency was 41.50%in the ICPP group,and that was 30%in the normal control group,the OR is 1.579(95%CI 1.047?2.382,P<0.05),the higher proportion of genotype distribution between the case and control group were respectively Rr and RR,respectively accounted for 51%and 48%.4.2 Alu? restriction site polymorphism analysis Frequency distribution of Alu? genotype and A allele between the two groups were not statistically significant(X2= 2.889,P=0.236;x2=2.749,P=0.097).The A allele frequency was 18.5%in the ICPP group,while that was 12.5%in the control group,the OR was 1.589(95%CI 0.916-2.755,P>0.05).The higher proportion genotype distribution between the two groups was aa genotype,respectively accounted for 66%and 76%.4.3 Rsa? and Alu? polymorphism combined analysis 9 haplotypes distribution by chi-square test was statistically significant(X2=15.821,P= 0.045)between the two groups.The constituent ratio of Rraa genotype in the ICPP group(39%)was higher than that in the control group(31%),while the proportion of rraa genotype(20%)in the ICPP group was lower than that in the control group(42%).5.ConclusionsRsa? and Alu? polymorphismsin ER 0 may be related with ICPP.The risk of ICPP in girls with allele R was 1.579(95%CI 1.047-2.382,P<0.05)fold of that with allele r.R allele may be a susceptible gene.Rr genotypemay be susceptible to ICPP.The Rraa genotype may be the potential risk factor for ICPP.