Study On The Genetic Risk Of Polycystic Ovary Syndrome And The Association Between The Gene LRP-5 Polymorphism And PCOS

Part one:The polycystic ovarian syndrome(PCOS)is a common endocrine metabolism disorder disease,it affects 5-10%reproductive-aged women. It is characterized by menstrual irregularities and biochemical and/or clinical hyperandrogenism such as hirsutism,seborrhoea and acne. Regardless of the presence of obesity,many are also insulin resistant.Its etilogy is still unknown.We can usually find female menses irregularity and male premature balding in first degree relatives of women with PCOS.The prevalence of menses irregularity arrives 50%.Considerable evidence indicates that PCOS is a multifactorial complex trait with polygenic components.The definite abnormal history is the risk factor. Familial aggregation of PCOS consistent with a genetic aetiology has been well documented in the literature.Western studies have found higher insulin resistance and TypeⅡDM as well as glucose tolerance disorder in the first degree relatives of PCOS patients compared to the control groups. This study was to investigate the phenotypes of the first relatives of PCOS,discussed the genetic risk of PCOS.Objective To explore the first degree relatives phenotypes in women with polycystic ovary syndrome(PCOS).Materials and methods Clinical data were collected by questionnaires from 105 first degree relatives of women with PCOS and from 103 first degree relatives of controls with normal menses from April 2007 to December 2007.It was compared for the distribution of male premature balding,female menses irregularity and parents' hypertension,diabetes,coronary heart disease,obesity between the first degree relatives of the PCOS group and the controls by chi-square tests. Falconer formula and SOLAR software were used to calculate the heritability of six phenotypes.Results There are significant differences between the incidence of obesity,diabetes and coronary heart disease.The prevalence of male premature balding and female menses irregularity,was significantly higher in PCOS group(19.1%,30.5%respectively)than in the controls (7.8%,1.9%respectively P＜0.01).The odds ratio was respectively 1.87, 2.958,3.541,2.794,22.137.The heritability was respectively 41.1%, 47.5%,48%,53.3%,87%.There is no significant difference between incidence of hypertension in two groups.And the heritability is 12%.Conclusion Compared with control group,the prevalence of the first degree relatives ' obesity,diabetes,coronary heart disease,male premature balding and female menses irregularity were significant higher in PCOS patients.Genetic factor is major in menses irregularity and the environment factor is more important in other phenotypes.Part two:It far confirmed that to PCOS patients specially to those with obesity, insulin resistance examination needs to be carried on as soon as possible to controlling obese occurrence and further aggravation.The family gather phenomenon of PCOS prompts heredity factor is the vital role in its pathogenesis.Symptom is difference in quantity among individualities, this characteristic hint PCOS possibly are caused by several main genes and environmental factor coactions.Until now the candidate genes which are being studied include genes participating insulin metabolism,sugar metabolism,fat metabolism,androgen metabolism and so on.Low-density lipoprotein receptor-related protein-5 has vital and remarkable role to glycometabolism and lipid metabolism.The gene LRP-5 polymorphism is associated with obesity phenotypes,especially with rs4988300(G/T) locus.But,gene LRP-5 polymorphism is at present no clear how to affect adiposis on the function.Adiposity is also one of common PCOS patient clinical manifestation.The prevalence of obesity in PCOS is about 40%.However,there are few studies in relationship between LRP-5 polymorphism and PCOS.Objective To investigate the association between the single nucleotide polymorphism(SNP)of the gene Low-density lipoprotein receptor-related protein-5(LRP-5)at rs34216038 and rs11574422 locus and polycystic ovarian syndrome(PCOS).Methods Denaturing High Performance Liquid Chromatography (DHPLC)was used to amplify the SNP of the gene LRP--5 at rs34216038 and rs11574422 locus for all 201 PCOS patients and the control group(109 healthy subjects).Comparisons were conducted in gene polymorphism between PCOS patients and control group.Results There are 2 unsymmetric figures in all 201 PCOS samples,2 unsymmetric figures in all 109 congtrol samples at rs11574422 locus.There is 1 unsymmetric figures in all 201 PCOS samples,no unsymmetric figure in all 109 control samples at rs34216038 locus,unsymmetric figures of PCR product were sequenced,we did not find heterozygous in rs11574422 locus but in cDNA(NM002335.2)1979.Conclusion The rs34216038 and rs11574422 are low frequency of single nucleotide polymorphism in Han PCOS patients and healthy people.There was no correlation with PCOS AND rs34216038, rs11574422,cDNA(NM002335.2)1979 may be a SNP locus.