Study Of Associated Genes With Polycystic Ovary Syndrome And Analysis Of Abnormal Glucose Tolerance

Objective Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases of women of fertile age. Insulin resistance (IR) has a crucial role in the pathogenesis of this disorder. There is evidence for a genetic component in PCOS based on familial clustering of cases . UrotensinⅡhas been found to be a potent vasoactive peptide in humans and may be implicated in the development of insulin resistance. The objective of this study was to investigate the distribution of the single nucleotide polymorphisms of rs228648 and rs2890565 in urotension 2(UTS2) gene in PCOS patients and controls in a Chinese population , to reveal biased transmission of two different allels from heterozygous parents to affected daughters,to analyze the association of two single nucleotide polymorphisms with the clinical, the hormone and metabolic characteristics of PCOS, and to evaluate genetic influence of the two SNPs of UTS2 gene on the development of PCOS.Methods 101 Chinese Han families trios consisting of fathers , mothers, affected daughters with PCOS are recruited .The affected patients with PCOS were recruited according to the revised diagnostic criteria, announced in the 2003 American Society for Reproductive Medicine/European Society for Human Reproduction and Embryology (ASRM/ESHRE) Roterdam consensus. 105 women were selected as healthy controls. The physiological and biochemical parameters including height,weight, abdominal and hip circumference, levels of serum follicular stimulating hormone (FSH), luteinizing hormone (LH), testosterone, fasting glucose and insulin are measured. DNA was extracted from human leukocyte nuclei isolated from whole blood. The genotypes of rs228648 and rs2890565 in urotensionⅡgene were determined through polymerase chain reaction Tm-shift genotyping method and were further confirmed by DNA sequence analyses.Results (1)There is no significant difference in age between the PCOS patient and the control groups. The levelof T ,LH,BMI,and WHR is significantly higher in the PCOS group than that in control group.The distribution of genotypic frequency of SNP rs228648 in controls, PCOS group and their parents group did not deviate from the Hardy-Weinberg equilibrium; The distribution of three genotype and two allelotypes of SNP rs228648 in urotension gene were similar between PCOS group and control group. Transmission disequilibrium test ( TDT)did not show significantly biased transmission of two different allels from parents to affected daughters at rs228648 locus( P > 0.05); No significant differences between the distributions of the SNP rs228648 polymorphisms were observed when PCOS-IR group and PCOS-NIR group were compared The same results were found in obese PCOS women compared to non-obese PCOS women. There was no significant difference of clinical, hormone,lipids metabolism characteristics of different genenotype of the SNP rs228648 in PCOS women , but the carriers with GG genotype of SNP rs228648(A/G) had significantly higher HOMA-IR compared to those with AA and AG genotypes( 2.33±2.06 vsl.83±1.08,P=0.038).(2) The distribution of genotypic frequency of SNP rs2890565 in PCOS group and their parents group and control group did not deviate from the Hardy-Weinberg equilibrium; The frequency of AA,AG,GG genotype of SNP rs2890565 in PCOS group was 10.89%, 42.57%,46.53% respectively, while in control group was4.76%, 32.38%,62.86% respectively. The distribution of genotype of SNP rs2890565 in urotension gene differed significantly between PCOS group and control group (P<0.05) .The frequency of A allele in PCOS group and control group was 32.18%,20.95%, while G allele was 67.82%,79.05%. The frequency of A allele of SNP rs2890565 in urotension gene was significantly higher in PCOS group than in control group (P<0.05) .TDT analysis showed an excess of A allele from heterozygous parents to affected offspring (P<0.05). The frequency of AA+AG genotype of SNP rs2890565 in PCOS-IR group and PCOS-NIR group was 63.6%, 41.3% respectively, while GG genotype was36.4%,58.7% respectively. The distribution of genotype of SNP rs2890565 in urotension gene differed significantly between PCOS-IR group and PCOS-NIR group (P<0.05) .The frequency of A allele in PCOS-IR group and PCOS-NIR group was 40.9%,21.7%, while G allele was 59.1%,78.3%. The distribution of two alleles of SNP rs2890565 in urotension gene was different between PCOS-IR group and PCOS-NIR group (P<0.05) . There was no significant difference of hormone,lipids metabolism characteristics of different genenotype of the SNP rs2890565 in PCOS women ,but the carriers with AA or AG genotype of SNP rs2890565(A/G) had significantly higher fasting plasma glucose(5.57±0.72 or 5.36±0.52 vs 4.02±0.59mmol/L, PO.05), higner fasting insulin(14.78±10.40 or 11.24±6.13 vs 9.57±5.23 U/L, P<0.05 ) compared to those with GG genotypes . HOMA-IR with AA genotype was significantly higher than those with GG genotype (3.53±2.76 vsl.82±1.25 P<0.05) .Conclusions There was no association of SNP rs228648 with clinical,hormone characteristics in PCOS women, but was found to be associated with insulin resistance in PCOS women. The genetic polymorphism of urotensionⅡgene rs2890565(A/G) may be associated with PCOS , the higher frequency of A allele was associated with insulin resistance in PCOS but had no association with obesity. Objective The objective of this study was to investigate the distribution of the single nucleotide polymorphism of rsl539355 in adiponectin receptor 1(ADIPOR1) gene in PCOS patients and controls in a Chinese population , to reveal biased transmission of two different allels from parents to affected daughters,to analysis the association of the single nucleotide polymorphism with the clinical, the hormone and metabolic characteristics of PCOS, and to evaluate genetic influence of the SNP of ADIPOR1gene on the development of PCOS.Methods 101 Chinese Han families trios consisting of fathers , mothers, affected daughters with PCOS were recruited .The affected patients with PCOS were recruited according to the revised diagnostic criteria, announced in the 2003 American Society for Reproductive Medicine/European Society for Human Reproduction and Embryology (ASRM/ESHRE) Roterdam consensus. 105 women were selected as healthy controls .The physiological and biochemical parameters including height,weight, abdominal and hip circumference, levels of serum follicular stimulating hormone (FSH), luteinizing hormone (LH), testosterone, fasting glucose and insulin were measured. DNA was extracted from human leukocyte nuclei isolated from whole blood. The genotypes of rs1539355 locus in ADIPOR1 gene were determined through polymerase chain reaction Tm-shift genotyping method and were further confirmed by DNA sequence analyses.Results There was no significant difference in age between the PCOS patients and the control group . The levelof T ,LH,BMI,and WHR was significantly higher in the PCOS group than that in control group.The distribution of genotypic frequency of SNP rs1539355 in controls, PCOS group and their parents group did not deviate from the Hardy-Weinberg equilibrium; The distribution of three genotype and two allelotypes of SNP rs1539355 inADIPOR1 gene were similar between PCOS group and control group. Transmission disequilibrium test ( TDT) did not show significantly biased transmission of two different allels from parents to affected daughters at rs1539355 locus( P > 0.05); (2) The frequency of AG+GG genotype of SNP rsl539355 in PCOS-IR group and PCOS-NIR group was 69.1%, 39.1% respectively, while AA genotype was30.9%,60.9% respectively. The distribution of genotype of SNP rsl539355 in urotension gene differed significantly between PCOS-IR group and PCOS-NIR group(P<0.05) .The frequency of A allele in PCOS-IR group and PCOS-NIR group was 61.8%,78.3%, while G allele was 38.2%,21.7%. The distribution of two alleles of SNP rs1539355 in ADIPOR1 gene were different between PCOS-IR group and PCOS-NIR group (P<0. 05) . The distribution of frequency of genotypes and alleles was similar in hyperandrogenism group and non- hyperandrogenism group,obese group and non-obese group (3) The carriers with G allele had higher body mass index (BMI) ( P<0. 05) and HOMA-IR ( P <0. 05) compared to AA genotype in the patients with PCOS.(26. 26±4.09 vs24. 13±3. 07 kg/m~2, 2.32±1.07 vs1. 85±0. 56) . A univariate general linear model analysis, introducing BMI as a covariate in the model, was perfomed , the results showed that SNP rsl539355 still influenced HOMA-IR( P <0.05).Conclusions SNP rs1539355 in ADIPOR1 gene was found to be associated with insulin resistance and had some influence on BMI, but there was no association with hormonal and lipid characteristics in PCOS women. Objective To analyse the prevalence of impaired glucose tolerance (IGT) and diabetes mellitus(NIDDM) in women with polycystic ovary syndrome and to identify associated risk factors within this population.Method Retrospective study was performed in 101 women with PCOS and clinical data were analysed after oral glucose tolerance tests to identify risk factors for abnormal glucose tolerance by using multivariate logistic regression.Results Based on the criteria for IGT and NIDDM, PCOS women were divided into two groups :77 cases with normal glucose tolerancr(NGT) and 24 cases with abnormal glucose tolerance. The prevalence for IGT was 21.8% and that of NIDDM was 1.98%. The mean age, body mass index(BMI), waist hip ratio(WHR), total testosterone, fasting plasma glucose, 2-h plasma glucose level were significantly different between AGT and NGT group(P<0.05). Fasting insulin, 2-h insulin, homeostasis model assessment of insulin resistance were significantly higher in AGT group(P＜0.01). Menarche age and LH/FSH made no difference between the two groups(P>0.05). The incidence of a family history of diabetes was higher in AGT patients(P<0.01). Multivariate logistic regression showed that age, BMI, , a family history of diabetes,fasting insulin levels were independent risk factors for AGT.Conclusion Women with PCOS are at increased risks for abnormal glucose metabolism. 2-h plasma glucose level after oral glucose toerance test was a significant predictor for abnormal glucose tolerance in women with PCOS. Age, BMI, a family history of diabetes, fasting insulin levels were independent risk factors for abnormal glucose tolerance.