| PartⅠEndocrine and Metabolic Characteristics of Polycystic Ovary Syndrome in Chinese Women with Different Phenotypes According to Menstrual Cycle Pattern and Body Mass IndexObjective:Known as a heterogeneous and complex disorder in women, polycystic ovary syndrome (PCOS) is a disease of oligomenorrhea or amenorrhea, androgen excess and polycystic ovaries. Studies on etiology, diagnosis and treatment of PCOS are difficult because of the heterogeneity. Moreover, ovulatory function is a pathologic feature in women with PCOS, and the menstrual cycle can serve as a convenient marker of ovulatory function. In addition,30% of PCOS patients are obese. Different metabolic risk profiles have also been observed between obese and lean women with PCOS. The increased incidence of long-term complications in PCOS women may parallel in the increase in obesity. The aim of this study was to identify the endocrine and metabolic characteristics of Chinese PCOS women with different menstrual cycle patterns and BMI, and to determine to what extent the subtypes affect these patients.METHODS:In the present study, we recruited 3539 patients with PCOS who visited the Center for Reproductive Medicine, Provincial Hospital Affiliated to Shandong University. And the 590 controls were women seeking infertility treatment and the reason of infertility had been established due to male factors and/or tubal disease. Anthropometric variables, endocrine and metabolic parameters were measured in all subjects. They were divided into three groups according to characteristics of the menstrual cycle. All of the patients were also divided into the following three sub-groups based on BMI:< 25kg/m2,25≤and≤30 kg/m2, and>30kg/m2.Endocrine and metabolic characteristics were compared among the PCOS subgroups.RESULTS:(1) In the PCOS group,95.28% of the patients (3372/3539) met the criteria for OA; 64.11% of the patients (2269/3539) met the criteria for HA and 95.73% of the patients (3388/3539) met the criteria for PCOs.The estimated prevalence of amenorrhea, oligomenorrhea, and eumenorrhea was 25.7%(911/3539), 69.5%(2461/3539),4.7%(167/3539), respectively. According to BMI, there were 53.69% of the patients (n=1900) in the<25kg/m2 group,33.29% of the patients (n=1178) in the 25kg/m2-30 kg/m2 group, and 13.03% of the patients (n=461) in the>30kg/m2 group. (2) The control group was older than the other 3 groups (P>0.001) but had the lowest BMI (P<0.001). The minimum waist-to-hip ratio (WHR) existed in the eumenorrhea group (P=0.006). In the 3 subgroups based on BMI, patients with a BMI<25kg/m2 were the youngest (P<0.001). The WC, mF-G scores, and WHR increased following the change in BMI after adjusting for age (P<0.05). (3) Compared with the three groups categorized by menstrual cycle, the control group had the lowest levels of FSH, LH, LH/FSH, PRL, T, TC, TQ LDL, and non-HDL after adjustment age and BMI(P<0.05). The levels of serum testosterone, LH and OGTT 2h glucose were relatively increased in the amenorrhea group (P<0.05). (4)The triglycerides, and LDL levels were the highest in the amenorrhea group (P<0.05). The same trend existed in TC and non-HDL levels, although there was no statistical significance (P>0.05). (5) Subjects with BMI<25 kg/m2 had higher values of FSH, LH, LH/FSH, and PRL (P<0.001) than the other two groups. The levels of TQ LDL, and non-HDL, and the indices of glucose and insulin metabolism increased with the change in BMI (P<0.001) CONCLUSIONS:(1) PCOS patients with different patterns of menstrual cycle showed diverse clinical manifestations, endocrine and metabolic characteristics, so the choice of treatment should be individualized. (2) The amenorrhea group had endocrine and metabolic abnormalities, which appeared to be related to latent long-term complications and higher morbidity. (3) The degree of dysbolism was positively associated with the change in BMI. PartⅡClinical and Metabolic Characteristics of the Parents of Women with Polycystic Ovary Syndrome Accompanied by HyperandrogenismObjective Different phenotypes of PCOS were associated with dissimilar endocrine and metabolic characteristics. PCOS is a polygene inheritance disease and has strong familial clustering, suggesting that PCOS may be a genetic disease. And elevated testosterone levels and polycystic ovaries are autosomal dominant heredity. The aim of this research was to analyze endocrine and metabolic characteristics in the parents of women with polycystic ovary syndrome accompanied by hyperandrogenism and to provide evidence in order to further understand the mode of inheritance for PCOS.Methods:PCOS probands were recruited from the Center for Reproductive Medicine, Shandong Provincial Hospital affiliated to Shandong University during the period from July 2007 to February 2010. A total of 226 PCOS family trios (parents and proband,678 members) were ascertained who were Han Chinese origins. Parents were divided into two groups based on different androgen levels of women with PCOS:group A, fathers of PCOS patients with hyperandrogenism (n=156); group B, fathers of PCOS patients without hyperandrogenism (n=70); group C, mothers of PCOS patients with hyperandrogenism (n=156); group D, mothers of PCOS patients without hyperandrogenism (n=70). The following available data were analyzed in the parents, respectively:age, body height, body mass index (BMI), waist-to-hip ratio (WHR), systolic and diastolic pressure, fasting blood glucose, and blood lipid levels, et al.Results There were no statistical differences between group A and group B in age, body height, weight, BMI, WC, HC, SBP and DBP (P>0.05). There were significantly higher WHR (0.92±0.06 vs.0.90±0.07, P=0.015) in group A than in group B. Low-density lipoprotein (2.75±0.82 vs.2.52±0.75, P=0.043) and TC levels(5.10±1.03 vs.4.81±0.82, P=0.039) were significantly higher in group A than in group B. In addition, significantly higher rate of hypertension was observed in group A than in group B. However, no differences were observed in the rates of PMPB, diabetes, cardiovascular disease (CD) and cerebrovascular disease (CVD) (P>0.05). And there were no significant differences between group C amd group D in the rates of hirsutism, irregular menstruation, history of infertility, hypertension, diabetes, CD and CVD (P>0.05). While no statistical difference was observed between groups C and D in endocrine and metabolic characteristics (P>0.05). There was a positive correlation between LDL levels in HA proband daughters with PCOS and fathers’ WHR (r=0.251, P=0.003, n=137), LDL levels (r=0.411, P<0.001, n=136) and mothers’ LDL(r=0.533, P<0.001, n=143), TC levels (r=0.317, P<0.001, n=143). In a multivariate regression analysis, the predictors of LDL levels in HA proband daughters were their fathers’ WHR, LDL levels and mothers’ TC levels (r2=0.352, P <0.001,n=134).Conclusions Paternal hypertension and lipid metabolism was found to be closely related to proband HA status. Low-density lipoprotein levels were increased in fathers of PCOS patients with hyperandrogenism which might be consistent with a heritable trait. The prevalence of hypertension was increased in fathers of PCOS patients with hyperandrogenism. PartⅢFamily association study between INSR gene polymorphisms and poly cystic ovary syndrome in a Chinese populationObjective:The syndrome is often associated with hyperinsulinemia, insulin resistance, type 2 diabetes, obesity, dyslipidemia, and cardiovascular diseases. Previous studies have observed that PCOS is a polygene inheritance disease and has strong familial clustering, suggesting that PCOS may be a genetic disease. Over the past decades, a number of candidate genes involved in insulin signaling pathway, steroid hormone synthesis, gonadotropin secretion and chronic inflammation have been performed to identify the susceptibility genes for PCOS. However, the mode of inheritance for PCOS and the molecular mechanisms underlying PCOS have not been clarified. Several factors would complicate the molecular genetics of PCOS, such as population stratification, environmental factors and genetic heterogeneity. To be a profound component of PCOS, insulin resistance earned much attention and genes involved in insulin action have been considered good candidates in explaining PCOS. Family-based analysis was performed using the transmission disequilibrium test (TDT) to assess the association between single nucleotide polymorphisms (SNPs) in the insulin receptor (INSR) gene and PCOS. This method is not influenced by population stratification or genetic heterogeneity and environmental contributions.Methods:PCOS probands were recruited from the Center for Reproductive Medicine, Shandong Provincial Hospital affiliated to Shandong University during the period from July 2007 to February 2010. A total of 260 PCOS family trios [one affected daughter (proband) and both parents,780 members] were ascertained who were Han Chinese origins. All the parents were randomly mated and there were no kinship among these pedigrees. A 5ml whole-blood sample was collected for each subject and stored in -80℃.. Genomic DNA was extracted using a TIANamp genomic DNA Kit (TIANGEN, Beijing, China) according to the manufacturer’s protocol. Four SNPs (rsl799817, rs2059807, rs8108622 and rs10500204) of INSR gene were amplified by polymerase chain reaction (PCR) and then directly sequenced to screen variants.RESULTS:(1)The four SNPs were in Hardy-Weinberg equilibriumin(P>0.05); (2) Rs8108622 and rs10500204 were in strong LD (r2= 0.93, D’=0.965); (3)Using the transmission disequilibrium test (TDT), we failed to find that rs1799817 (x2=0.486, p=0.486), rs2059807 (x2=1.681, p=0.195), rs8108622 (x2=0.029, p=0.866) and rs10500204 (x2=0, p=1.0) were significantly overtransmitted to PCOS offspring from their parents. (4)Similarly, the analysis of the haplotypes did not show evidence of association between these polymorphisms and PCOS (P>0.05).CONCLUSION:(1) No significant evidence of association or linkage was found at any of the markers tested, indicating that the INSR gene is unlikely to play a major role in the etiology of PCOS in our sample. (2) Because of the highly polymorphic of INSR molecule, further investigations are needed to address the contribution of other SNPs and several polymorphisms in the form of haplotypes. |
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