To determine the (tttta)n repeat polymorphisms at the promoter region of CYP11alpha gene, and study its linkage to hyperandrogenism of polycystic ovary syndrome (PCOS) in Chinese women, a case-control study was conducted in the Reproductive Medical Center of the Second Affiliated Hospital of Zhengzhou University (Zhengzhou, China). 96 PCOS patients and 78 healthy control women were included. CYP11alpha (tttta)n repeat-polymorphism genotyping analysis was performed by using polymerase chain reaction (PCR). Serum pituitary hormone and total testosterone levels were measured by ELISA. 4 different CYP11alpha (tttta)n allelles were identified, corresponding to 4-, 6-, 8-, and 9-repeat-unit alleles. The frequency and distribution of these alleles are 0.16, 0.33, 0.38, and 0.13 respectively in PCOS patients, as compared with 0.20, 0.34, 0.35, and 0.11 respectively in healthy controls. There were no significant differences between these two groups. Moreover, no correlation between the polymorphism of CYP11alpha gene and serum testosterone level of patients with PCOS and controls was observed. It is concluded that microsatellite polymorphism (tttta)n of gene CYP11alpha exists in Chinese women and the polymorphism of CYP11alpha gene does not play an important role in the pathogenesis of Chinese patients with PCOS, especially in patients with hyperandrogenism.
Cholesterol Side-Chain Cleavage Enzyme/*genetics ; Hyperandrogenism/complications ; Hyperandrogenism/*genetics ; Microsatellite Repeats ; Polycystic Ovary Syndrome/complications ; Polycystic Ovary Syndrome/*genetics ; *Polymorphism, Genetic/genetics

BACKGROUNDPolycystic ovary syndrome (PCOS) is the commonest endocrinopathy in women of reproductive age. The patients often develop insulin resistance (IR) or hyperinsulinemia despite manifesting anovulation and signs of hyperandrogenism. The cause and effect relationship of hyperinsulinemia and hyperandrogenemia (HA) is still debated. Micro-ribonucleic acids (miRNAs) have recently been shown to play a role in regulation of ovarian function. Our current study focused on the altered expression of miRNAs with PCOS.

METHODSOvarian theca interna tissues were obtained from 10 PCOS patients and 8 controls that were non-PCOS and had normal insulin sensitivity undergoing laparoscopy and/or ovarian wedge resection. Total RNA of all samples was extracted. We studied the repertoire of miRNAs in both PCOS and non-PCOS women by microarray hybridization. Bioinformatic analysis was performed for predicting targets of the differentially expressed miRNAs. Furthermore, selected miRNAs were validated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR).

RESULTSA total of 27 miRNAs were differentially expressed in PCOS patients with respect to the controls in our discovery evaluationand two (miR-92a and miR-92b) of them were significantly downregulated in PCOS women in followed validation (P < 0.05). Targets prediction revealed that miR-92a targeted both GATA family of zinc finger transcription factor GATA-binding factor 6 (GATA6) and insulin receptor substrate proteins 2 (IRS-2).

CONCLUSIONSMiRNAs are differentially expressed between PCOS patients and controls. We identified and validated two miRNAs-miR-92a and miR-92b. They are significantly downregulated and may be involved in the pathogenesis of PCOS.

Adult ; Female ; Humans ; Hyperandrogenism ; genetics ; Insulin Resistance ; genetics ; physiology ; Male ; MicroRNAs ; genetics ; Ovary ; metabolism ; Polycystic Ovary Syndrome ; genetics

OBJECTIVETo analyze genomic copy number variations (CNVs) in two sisters with primary amenorrhea and hyperandrogenism.

METHODSG-banding was performed for karyotype analysis. The whole genome of the two sisters were scanned and analyzed by array-based comparative genomic hybridization (array-CGH). The results were confirmed with real-time quantitative PCR (RT-qPCR).

RESULTSNo abnormality was found by conventional G-banded chromosome analysis. Array-CGH has identified 11 identical CNVs from the sisters which, however, overlapped with CNVs reported by the Database of Genomic Variants (http://projects.tcag.ca/variation/). Therefore, they are likely to be benign. In addition, a -8.44 Mb 9p11.1-p13.1 duplication (38,561,587-47,002,387 bp, hg18) and a -80.9 kb 4q13.2 deletion (70,183,990-70,264,889 bp, hg18) were also detected in the elder and younger sister, respectively. The relationship between such CNVs and primary amenorrhea and hyperandrogenism was however uncertain. RT-qPCR results were in accordance with array-CGH.

CONCLUSIONTwo CNVs were detected in two sisters by array-CGH, for which further studies are needed to clarify their correlation with primary amenorrhea and hyperandrogenism.

Amenorrhea ; diagnosis ; genetics ; Chromosomes, Human, Pair 4 ; genetics ; Chromosomes, Human, Pair 9 ; genetics ; Comparative Genomic Hybridization ; methods ; DNA Copy Number Variations ; genetics ; Female ; Humans ; Hyperandrogenism ; diagnosis ; genetics ; Karyotyping ; Reverse Transcriptase Polymerase Chain Reaction ; Siblings ; Young Adult

OBJECTIVETo assess the association between FEM1A gene polymorphisms and polycystic ovary syndrome (PCOS) in Chinese Han patients.

METHODSDNA sequencing was utilized to determine the genotypes of rs12460989 and rs8111933 loci of FEM1A gene in 120 PCOS patients and 155 healthy controls. Association between above polymorphisms and hyperandrogenism and insulin resistance (IR) was assessed.

RESULTSGenotypes TT, TG and GG of the rs12460989 locus, and GG, GC and CC of the rs8111933 locus were detected. There were significant differences in allelic frequencies (Chi square= 33.302, P< 0.01; Chi square = 11.252, P<0.01, respectively) for above loci between the two groups. Multifactorial logistic regression analysis indicated that TG+GG genotype of rs12460989 and GC+CC genotype of rs8111933 were included into the main effect model of hyperandrogenism, and GC+CC genotype of rs8111933 was included into the main effect model of IR.

CONCLUSIONParticular genotypes of the rs12460989 and rs8111933 loci of FEM1A gene are associated with PCOS in Chinese Han and may be a potential risk factor of hyperandrogenism. Polymorphisms of the rs8111933 locus of FEM1A gene may be a risk factor of IR.

Adult ; Asian Continental Ancestry Group ; Base Sequence ; Cell Cycle Proteins ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Hyperandrogenism ; genetics ; Insulin Resistance ; genetics ; Molecular Sequence Data ; Polycystic Ovary Syndrome ; genetics ; Polymorphism, Genetic

OBJECTIVETo explore the association between the microsatellite polymorphism in the promoter region of CYP11 alpha gene and hyperandrogenism of polycystic ovary syndrome (PCOS).

METHODSEighty-six cases of PCOS and 50 normal women as controls were studied. Polymerase chain reaction and electrophoresis on polyacrylamide gel were employed to detect the polymorphism of CYP11 alpha gene and its frequency distribution. At the same time, the relationships of CYP11 alpha alleles to serum testosterone levels in PCOS were compared.

RESULTSFour different CYP11 alpha (tttta)n alleles were identified, corresponding to 4, 6, 8 and 9 repeat-units alleles. The frequency distribution profiles were 0.17, 0.31, 0.39, 0.13 and 0.22, 0.35, 0.33, 0.10 in PCOS group and control group respectively, showing no statistically significant difference between the two groups. There were no correlations between the polymorphism of CYP11 alpha gene and the serum testosterone levels of PCOS patients.

CONCLUSIONMicro-satellite polymorphism (tttta)n of gene CYP11 alpha exists in Chinese women and the polymorphism does not relate to the pathogenesis of hyperandrogenism in women with PCOS.

Adult ; Asian Continental Ancestry Group ; genetics ; China ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Hyperandrogenism ; etiology ; Male ; Microsatellite Repeats ; genetics ; Polycystic Ovary Syndrome ; complications ; ethnology ; genetics ; Polymerase Chain Reaction ; Polymorphism, Genetic ; genetics ; Steroid 11-beta-Hydroxylase ; genetics ; Young Adult