[Show abstract][Hide abstract] ABSTRACT: Following a previous genome-wide association study (GWAS 1) including 744 cases and 895 controls, we analyzed genome-wide association data from a new cohort of Han Chinese (GWAS 2) with 1,510 polycystic ovary syndrome (PCOS) cases and 2,016 controls. We followed up significantly associated signals identified in the combined results of GWAS 1 and 2 in a total of 8,226 cases and 7,578 controls. In addition to confirming the three loci we previously reported, we identify eight new PCOS association signals at P < 5 × 10(-8): 9q22.32, 11q22.1, 12q13.2, 12q14.3, 16q12.1, 19p13.3, 20q13.2 and a second independent signal at 2p16.3 (the FSHR gene). These PCOS association signals show evidence of enrichment for candidate genes related to insulin signaling, sexual hormone function and type 2 diabetes (T2D). Other candidate genes were related to calcium signaling and endocytosis. Our findings provide new insight and direction for discovering the biological mechanisms of PCOS.
[Show abstract][Hide abstract] ABSTRACT: Polycystic ovary syndrome (PCOS) and type 2 diabetes (T2D) are two common metabolic disorders in reproductive-aged women, and both are associated with insulin resistance. Evidence has indicated that the growth hormone receptor (GHR) exon 3 polymorphism is associated with T2D and the GHRd3 allele may have the preventive effect on the disease. However, the genetic effect of this polymorphism on PCOS is unknown. The present study thus aims to evaluate the association between the GHR exon 3 polymorphism and PCOS.
A total of 432 patients with PCOS and 441 healthy control subjects were included. All of them were Han Chinese women and well characterized. Genotyping experiments of GHR exon 3 polymorphism were performed with a standard protocol of PCR and gel electrophoresis.
GHRd3 allele frequency in PCOS patients was significantly higher compared to the control subjects (19.1% vs. 14.3%; P=0.007, OR=1.416; 95% CI=1.099-1.825). Further analyses indicated that the GHRd3 allele was associated with increased waist and hip circumstance in healthy women (P=0.016; 0.003), and also with 1-h, 2-h and area under the curve (AUC) plasma glucose levels among PCOS patients (all P<0.05). But, no association of GHR exon 3 polymorphism with insulin resistance in the patients was observed.
The present study provides the first evidence that GHR exon 3 polymorphism is associated with PCOS in Han Chinese women. The GHRd3 allele may contribute to an impact of glucose metabolism but not insulin resistance.
Growth hormone & IGF research: official journal of the Growth Hormone Research Society and the International IGF Research Society 08/2011; 21(5):248-51. · 2.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Polycystic ovary syndrome (PCOS) is a common metabolic disorder in women. To identify causative genes, we conducted a genome-wide association study (GWAS) of PCOS in Han Chinese. The discovery set included 744 PCOS cases and 895 controls; subsequent replications involved two independent cohorts (2,840 PCOS cases and 5,012 controls from northern Han Chinese; 498 cases and 780 controls from southern and central Han Chinese). We identified strong evidence of associations between PCOS and three loci: 2p16.3 (rs13405728; combined P-value by meta-analysis P(meta) = 7.55 × 10⁻²¹, odds ratio (OR) 0.71); 2p21 (rs13429458, P(meta) = 1.73 × 10⁻²³, OR 0.67); and 9q33.3 (rs2479106, P(meta) = 8.12 × 10⁻¹⁹, OR 1.34). These findings provide new insight into the pathogenesis of PCOS. Follow-up studies of the candidate genes in these regions are recommended.
[Show abstract][Hide abstract] ABSTRACT: To evaluate basal testosterone (T) levels during follicular phase of the menstrual cycle as a predictor for ovarian response and in vitro fertilization (IVF) outcome.
We analyzed data retrospectively from hospital-based IVF center including one thousand two hundred and sixty Chinese Han women under their first IVF cycle reached the ovum pick-up stage, without polycystic ovary syndrome (PCOS) or endometriosis undergoing long IVF protocol. Patients were divided into 2 groups. Group 1: patients with diminished ovarian reserve (basal FSH >10 IU/L) (n = 187); Group 2: patients with normal ovarian reserve (basal FSH < = 10 IU/L) (n = 1073). We studied the association of basal T levels with ovarian response and IVF outcome in the two groups. Long luteal down-regulation protocol was used in all patients, that is, the gonadotropin releasing hormone agonist was administered in the midluteal phase of the previous cycle and use of recombinant FSH was started when satisfactory pituitary desensitization was achieved.
Basal T levels were markly different between pregnant and non-pregnant women in Group 1; whereas not in Group 2. A testosterone level of 47.85 ng/dl was shown to predict pregnancy outcome with a sensitivity of 52.8% and specificity of 65.3%; and the basal T was correlated with the numbers of large follicles (> 14 mm) on HCG day in Group 1. Significantly negative correlations were observed between basal T, days of stimulation and total dose of gonadotropins after adjusting for confounding factors in both groups.
In women with diminished ovarian reserve, basal T level was a predictor for the number of large follicles on HCG day and pregnancy outcome; but could not in those with normal serum FSH. Basal T levels were associated with both days of stimulation and total dose of gonadotropins, indicating that lower level of T might relate with potential ovarian poor response.
Reproductive Biology and Endocrinology 01/2011; 9:9. · 2.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the effects of different proportions of cryoprotectant to seminal plasma on the motility of post-thaw human sperm.
Different proportions of cryoprotectant to seminal plasma (1:1 and 1:3) were used for freezing sperm, and the forward movement and total motility rates of the frozen-thawed sperm were compared.
The forward movement and total motility rates were (58.60 +/- 5.57)% and (66.17 +/- 5.24)% before cryopreservation. The 1:1 proportion achieved post-thaw forward movement and total motility rates of (40.53 +/- 8.97)% and (51.23 +/- 9. 30)%, while the 1:3 (44.7 +/- 8.67)% and (51.50 +/- 7.40)%, respectively. Significantly decreased sperm motility was observed after cryopreservation (P < 0.05). Statistically significant differences were found in the forward movement but not in the total motility of the frozen-thawed sperm between the two proportions.
Cryopreservation causes obvious damage to human sperm. Higher proportion of cryoprotectant to seminal plasma (1:3) can improve the forward movement of post-thaw sperm as compared with the lower one (1:1).
Zhonghua nan ke xue = National journal of andrology 05/2009; 15(5):422-4.
[Show abstract][Hide abstract] ABSTRACT: To analyze the clinical and metabolic characteristics of large-scale Chinese women with polycystic ovary syndrome (PCOS).
Hospital-based IVF center.
Patients with PCOS.
In the present study, one thousand and forty PCOS patients were selected from women who visited the Reproductive Medicine Center at Shandong Provincial Hospital Shandong University between January 2002 and December 2006. All the patients had been performed a 75 g OGTT. Clinical characteristics, serum hormonal levels, glucose levels, insulin levels and lipid profiles were reviewed.
An oral glucose tolerance test and insulin release test were performed for each woman. After overnight fasting, blood samples were collected to determine fasting blood glucose, blood glucose and insulin (30 min, 60 min, 120 min, 180 min) after digesting 75 g glucose, luteotrophic hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), prolactin (PRL), estradiol (E2), and blood lipid levels.
Height, weight, waistline, hip circumference, F-G grade for hirsutism, gonadal hormone results, blood lipid level, blood glucose tolerance, each-moment insulin level, and family history were determined.
(i) The presence of oligomenorrhea was 62.6% while amenorrhea was 19.71%. Menstrual disorder of all the adult patients could be traced back to their adolescent menarche. There were 450 obesity cases of which 259 patients were central obesity. The incidence of acanthosis nigricans was 15.19%, 65.19% with obesity. (ii) Cholesterol (4.8 +/- 0.98 vs 4.61 +/- 0.86) and LDL (3.80 +/- 6.92 vs 2.88 +/- 1.01) were both significantly higher in the obesity patients than the non obesity patients. (iii) 173 patients were diagnosed as diabetes mellitus (DM), 179 IGT, 27 IFG and 9 (IFG and IGT). Those women with plasma glucose values abnormality of 0, 30 min, 60 min, 120 min, 180 min were 19 cases 0.98% (19/173), 74 cases 42.77% (74/173), 110 cases 63.58% (110/173), 42 cases 24.28% (42/173) and 12 cases 6.94% (12/173) respectively. Ten (10/173) patients would have been undetected if fasting plasma glucose levels were not evaluated, while omission of 30 min, 60 min, 120 min, or 180 min plasma glucose levels would have resulted in 16 cases (16/173), 50 cases (50/173), 28 cases (28/173) and 1 case (1/173) being missed respectively. If we took three times blood samples to evaluate plasma glucose levels, 39 cases (39/173) (0 min + 30 min +60 min), 102 cases (0 min + 30 min + 120 min), 21 cases (0 min + 30 min + 180 min), 34 cases (0 min + 60 min + 120 min), 45 cases (0 min + 60 min + 180 min), 123 cases (0 min + 120 min + 180 min) would be missed. Compared AUC of plasma glucose and insulin in 5 times with 3 times (0 min + 30 min + 60 min), the differences were statistically significant. Body mass index (BMI) was positively correlated with HOMA-IR (r = 0.29987 (P<0.01) as well as WHR (r = 0.12441, P<0.0001).
(i) The prevalence rate of obesity was higher in PCOS. The state of obesity had a positive relation with insulin resistance. (ii) The prevalence rate of lipid profiles abnormality in obesity group was higher than in non-obesity. (iii) OGTT was the essential examination for all the PCOS patients.
[Show abstract][Hide abstract] ABSTRACT: To determine a suitable standard of hirsutism for Chinese polycystic ovary syndrome (PCOS) patients living in Shandong region.
A total of 623 unbiased women from the general population in Jinan city, 131 PCOS patients and 84 controls from outpatients in Shandong region were studied with questionnaires, physical and pelvic ultrasound examination, body hair on 11 sites were evaluated, and 9 (lip, chin, arm, thigh, chest, upperbelly, lowerbelly, upperback, lowback) of them which were called hormone Ferriman-Gallwey (F-G) score and 2 (forearm, leg) sites of indifferent hormone score were calculated according to the score system described by Ferriman and Gallwey.
(1) Both body hair F-G score and indifferent hormone score distribution mode in the <or= 40 years old population were un-normal and both the 95th percentages of score were 2. (2) The hirsutism was significantly higher in PCOS patients [48.1% (63/131)] than in controls [4.8% (4/84)] by F-G score >or= 2 (chi(2) = 47.68, P < 0.01), but no statistic difference by F-G score >or= 6 criterion (chi(2) = 0.64, P = 0.42). (3) F-G scores were declined with age increase. The hair score on the lip, chest, lowerbelly in general population were positively correlated with F-G score (r = 0.712, 0.594, 0.522; P < 0.01) and in PCOS patients (r = 0.879, 0.682, 0.710; P < 0.01), and on the lip in controls (r = 0.950, P < 0.01). (4) The correlation contingency coefficient between hirsutism (F-G score >or= 2) and lip, chest, lowerbelly site in general population was 0.461, 0.420, 0.489 and was 0.560, 0.532, 0.503 in PCOS group respectively.
(1) Both body hair F-G score and indifferent hormone score distribution mode are significantly different from Ferriman-Gallwey's report; according to our investigation the suitable criterion of hirsutism for Chinese women in Shandong region should be >or= 2 scores. (2) By F-G score >or= 2 standard, hirsutism is more common in PCOS than in control. (3) Lip, chest, and lowerbelly are the main sites to determine the hirsutism status of women, and the later two sites are more specific for PCOS hirsutism. Forearm and leg score can indicate hirsutism status in some degree but are not specific and sensitive for PCOS hirsutism.
[Show abstract][Hide abstract] ABSTRACT: To carry out an epidemiological study of clinical characteristics of Chinese Han ethnic women with polycystic ovary syndrome (PCOS).
According to Revised 2003 European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine criteria, PCOS can be diagnosed with 2 manifestations out of oligo-or anovulation, clinical and/or biochemical signs of hyperandrogenism exclusion of other etiologies and polycystic ovaries. One thousand and twenty-seven women in reproductive age from one area in Jinan city were investigated and the clinical, metabolic characteristics of the PCOS patients were analyzed.
(1) A total of 828 questionnaires were collected from 1027 women; the response rate was 80.62%. Eighty-five PCOS patients were diagnosed; PCOS accounted for 97.65% (83/85) in <or= 35 years old population groups; (2) Clinical manifestations were different between PCOS groups and controls in each age stage (P < 0.05); Menstruation, body hair Ferriman-Gallny (F-G) score, acne, ovarian follicle numbers decreased with aging among PCOS groups, and menstruation cycle was longer, testosterone (T), free androgen index (FAI) and ovarian follicle numbers were higher, sex hormone-binding globulin (SHBG) was lower than control groups of the same age respectively (P < 0.01); (3) Homeostasis model assessment-insulin resistance (Homa-IR) index in infertility PCOS group was higher than in fertility group (1.49 +/- 0.73 vs 1.31 +/- 0.66; t = 2.058; P < 0.05); fasting insulin, fasting blood glucose in obesity PCOS group was higher than in non-obesity group (8.50 +/- 3.46 vs 5.7 +/- 2.3, t = 2.984; P < 0.01, 5.45 +/- 0.54 vs 4.88 +/- 0.45, t = 2.891; P < 0.01), in contrast, insulin sensitivity index was lower in obesity PCOS group than in non-obesity group (0.025 +/- 0.015 vs 0.044 +/- 0.026; t = 2.292, P < 0.05).
(1) PCOS mainly distributes in <or= 35 years old population; (2) clinical manifestations of oligo-ovulation, clinical and/or biochemical signs of hyperandrogenism, polycystic ovaries of PCOS change with age increase. (3) PCOS with infertility and obesity is usually associated with glucose metabolic changes, especially insulin resistance.