Series Studys On The Chinese Polycystic Ovary Syndrome Related Factors

Section I :THE RELATIONSHIP BETWEEN BODY MASS INDEX,ENDOCRINE AND METABOLISM MARKERS OF ATIENTSWITH POLYCYSTIC OVARY SYNDROMEObjective: The aim of this paper was to analysis the body mass index, endocrine, blood sugar, insulin and lipid of the patients with polycystic ovary syndrome, further to understand these markers in the PCOS and provide evidence in order to correctly diagnosis and therapy the PCOS.Methods: 120 cases with PCOS diagnosed in Shandong Provincial Hospital between Jan and May in 2003 were randomly selected. Body height and body weight were measured, the body mass index (BMI) were calculated according to the formula (body mass index=body weight (kg)/ (body height) ~2(m~2)). Endocrine and insulin levels were measured using chemiluminescence's methods. Blood lipid and sugar were measured using biochemical equipment. Then the patients were divided into different groups according to different markers, the results were compared between the different groups.Results: (1) The PCOS patients were divided into two groups according to the BMI. The fasting blood sugar and insulin levels, 30 min, 60 min, 120 min sugar and insulin levels after 75g glucose load of the obese PCOS group (BMI≥25kg/m~2) were higher than those of the lean PCOS group, the insulin resistance index of the obese PCOS group was higher than that of the lean PCOS group, while insulin sensitiveindex was lower. Luteinizint hormone of the lean PCOS group was higher than that of the obese PCOS group. All the differences were significant (P<0.05); (2) The PCOS patients were divided into two groups according to the insulin levels. The BMI of the insulin resistance group was higher than that of the group without insulin resistance, the difference between the two groups was extremely notable (P<0.001); The fasting blood sugar and insulin levels, 30 min, 60 min, 120 min sugar and insulin levels after 75g glucose load of the insulin resistance group increased more obviously than that of the group without insulin resistance. (3) The PCOS patients were divided into two groups according to the fasting testosterone levels. The fasting insulin level and 60 min insulin level after glucose loading of the hyperandrogenemia group were higher than that of the group without hyperandrogenemia, the insulin sensitive index of the hyperandrogenemia were also higher, while the insulin resistance index lower. The estradiol, LH, testosterone levels of the hyperandrogenemia group were higher than that of the group without hyperandrogenemia, the differences were significant(P <0.05). The relationship between the testosterone level and estradiol level was positive line correction (Pearson correlation radio was 0.325, P=0.003), and the relationship between the testosterone and LH was too (Pearson correlation radio was 0.298, P=0.006). Regarding that BMI might influence the testosterone and estradiol levels, the partial correction between the testosterone and LH, testosterone and estradiol were analysed after controlling the BMI, and the results were positive correction.Conclusions: 1 The obese PCOS patients are easier to present insulin resistance, body weight plays a role in the occurrence of insulin resistance; 2 Insulin resistance and hyperandrogenemia of PCOS are correlated, they influence each other; 3 LH, estradiol and testosterone levels are positive correlation, they have nothing to do with the BMI.Section II:SINGLE NUCLEOTIDE POLYMORPHISM IN THEINSULIN RECEPTOR GENE AND THE CHINESEPOLYCYSTIC OVARYSYNDROMEObjective: To investigate the relationship between single nucleotide polymorphism at 17 exon in tyrosine kinase domain of the insulin receptor gene and Chinese polycystic ovary syndrome (PCOS), and the role of insulin receptor gene in the pathogenesis of PCOS.Methods: Single nucleotide polymorphism of the 17 exon in tyrosine kinase domain of the insulin receptor gene in 120 cases with PCOS and 40 normal cases as controls were measured with modified polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The levels of follicular stimulating hormone, luteinizing hormone, prolactin, estradiol, testosterone and lipid in the basal state were measured, glucose tolerance and insulin releasing before and after 75g glucose loading were also assayed.Results: (1) According to the BMI, patients with PCOS were divided into two groups: the obese (BMI>25kg/m2) and the lean (BMK25kg/m2). The blood sugar and insulin levels of fasting ,30 min , 60 min, 120 min of the obese group after glucose loading were higher than those of the lean group(P<0.05). Polymorphism frequency of occurrence of the exon 17 of INSR in patients with PCOS (41%) was higher than that in the normal female (12.5%). There was significant difference between the lean group (52%) and the obese group (25%)(P<0.05), between the lean group and the normal female. But there was no statistic difference between the obese group and the normal female(P>0.05). (2) According to the polymorphism frequency of occurrence of the exon 17 of INSR, patients were divided into two groups: T group, which means the 1058 site of the exon 17 of INSR is thymine, while C group is cytosine. The BMI of T group was lower than that of the C group, but the two groups' blood sugar, lipid and insulin were similar, the differences were not significant (P> 0.05). (3) The polymorphism frequency in the exon 17 of INSR was not different between the insulin resistance group and without insulin resistance group. (4) The polymorphism frequency in the exon 17 of INSR was not statistic difference betweenthe hyperandrogenemia group and without hyperandrogenemia group.Conclusions: Single Nucleotide Polymorphism in the exon 17 of INSR is associated with Chinese Polycystic Ovary Syndrome; T allele higher occurrence frequency is one of the characters of the lean PCOS, and the exon 17 of INSR might be label gene of the lean PCOS. However, this polymorphism is not associated with the PCOS common abnormal such as insulin resistance, hyperandrogenemia, so we can think this polymorphism in the exon 17 of INSR is not a special functional gene polymorphism.Section III:STUDY ON THE INTRON 2 OF RESISTIN GENE OF THE POLYCYSTIC OVARY SYNDROMEObjective: Polycystic ovary syndrome (PCOS) was a leading cause of anovulatory infertility and affects approximately 5~10% of reproductive age women. It was characterized by hyperandrogenemia and chronic anovulation and is associated with insulin resistance, obesity, and increased risk for type 2 diabetes. In a screen of candidate genes, a region on chromosome 19p13.3 was identified that shows significant evidence for both linkage and association with PCOS. A promising candidate gene for PCOS, resistin, maps to exactly this region. Resistin, a recently discovered protein hormone, thought to modulate glucose tolerance and insulin action, may play a part in the pathogenesis of insulin resistance. The aim of this study was to investigate whether the intron 2 of resistin gene had polymorphisms and was associated with polycystic ovary syndrome through sequencing the resistin gene intron 2 of the PCOS patients and normal controls.Methods: We sequenced 75 PCOS patients and 66 normal controls for association with a single nucleotide polymorphism in the intron 2 of the resistin gene by using Genetic Analyzer. And we measured the endocrine levels such as follicle stimulating hormone, luteinizint hormone, prolactin, estradiol, and testosterone. Then we compared the results of the PCOS patients and the normal controls.Results: We for the first time found that the 39 site from the terminal exon 2 of the resistin gene had a single nucleotide polymorphism: Cytosine or Cytosine Thymine cannula cusp. And we did not find the variant from C to T in this site. The C allele frequency of the PCOS patients was 0.96(72/75), CT cannula cusp frequency was 0.04(3/75), and the C allele frequency of the normal controls was 0.95(63/66), the CT cannula cusp frequency 0.05(3/66), the difference was not significant (P>0.05). It was therefore unlikely that variation in the resistin gene accounts for the strong association that we observe between resistin gene and PCOS. The FSH, PRL, E2 levels were similar in PCOS patients and controls while the LH and T levels were higher in the PCOS patients than in the normal controls.