Association of single-nucleotide polymorphisms rs2197076 and rs2241883 of <Emphasis Type="Italic">FABP1</Emphasis> gene with polycystic ovary syndrome

Purpose

The objective of this study was to evaluate the association between single-nucleotide polymorphisms (SNPs) rs2197076 and rs2241883 in fatty acid-binding protein 1 (FABP1) gene and polycystic ovary syndrome (PCOS).

Methods

The two alleles rs2197076 and rs2241883 in FABP1 gene in 221 PCOS women and 198 normal women were amplified and sequenced. Allele frequency comparison was performed between the PCOS and control groups, and genotype-phenotype correlation analysis was performed using dominant and recessive models to assess the association of FABP1 and the main features of PCOS.

Results

Allele frequency analyses showed a strong association of SNPs rs2197076 and rs2241883 of FABP1 gene with PCOS (P < 0.001). The additive, dominant, and recessive genotype model analyses further supported this association even after adjusting for age and body mass index (BMI). The minor allele frequency (MAF) of rs2241883 in obese PCOS women was less than that in obese control women. Further genotype-phenotype correlation analysis showed that SNP rs2197076 had a stronger association with the main features of PCOS than SNP rs2241883.

Conclusion

In the association of SNPs in FABP1 gene with PCOS, rs2197076 was more closely associated with its main features than rs2241883 and seemed to play a more important role in the pathogenesis of PCOS.     

Silver-Russell syndrome in a girl born after <Emphasis Type="Italic">in vitro</Emphasis> fertilization: partial hypermethylation at the differentially methylated region of <Emphasis Type="Italic">PEG1</Emphasis>/<Emphasis Type="Italic">MEST</Emphasis>

Purpose: The prevalence of low birth weight (LBW) is increased in subjects born after assisted reproduction technology (ART), and defective imprinting has frequently been identified in patients with Beckwith-Wiedermann and Angelman syndromes conceived by ART. Thus, we examined methylation pattern in a girl born after ART who had Silver-Russell syndrome (SRS) which can be caused by maternal uniparental disomy for chromosome 7 and by hypomethylation of the differentially methylated region (DMR) of H19. Methods: We examined methylation status of 31 cytosines at the CpG dinucleotides in the DMR of PEG1/MEST on 7q32.2 and 23 cytosines at the CpG dinucleotides in the DMR of H19 on 11p15, using leukocyte genomic DNA. Results: Eight of the 31 cytosines in the patient and four of the 31 cytosines in the father were hypermethylated in the PEG1/MEST-DMR. In the H19-DMR, no abnormal methylation pattern was identified in the patient. Conclusion: The results suggest that hypermethylation of paternally expressed genes including PEG1/MEST, which usually have growth-promoting effects, may be relevant to LBW in subjects conceived by ART. Partial hypermethylation was identified at the differentially methylated region of paternally expressed PEG1/MEST in a girl with Silver-Russell syndrome born after in vitro fertilization.     

MicroRNA expression in preimplantation mouse embryos from <Emphasis Type="Italic">Ped</Emphasis> gene positive compared to <Emphasis Type="Italic">Ped</Emphasis> gene negative mice

PURPOSE: The mouse preimplantation embryo development (Ped) gene product, Qa-2, influences the rate of preimplantation embryonic development and overall reproductive success. Here we investigated the expression pattern of two microRNAs, miR-125a and miR-125b, known to be involved in development in lower organisms, in preimplantation embryos from the two-cell, four-cell, eight-cell, morula, and blastocyst stages of development from the congenic B6.K1 (Ped negative) and B6.K2 (Ped positive) strains of mice. METHOD: B6.K1 and B6.K2 congenic mice differ only in the absence (B6.K1) or presence (B6.K2) of the genes encoding Qa-2 protein. We analyzed the expression of miR-125a and miR-125b in B6.K1 and B6.K2 preimplantation embryos by using real-time PCR. RESULT: We found no variability in miR-125b expression at any developmental stage in both strains. However, miR-125a expression increased during development in both strains and was ten times higher in Ped negative (B6.K1) embryos than in Ped positive (B6.K2) embryos by the blastocyst stage of development. CONCLUSION: Our results show that the absence of the Ped gene profoundly affects the level of a miRNA (miR-125a) known to regulate early development. The implication is that miR-125a is likely involved in the regulation of timing of early development in mice.     

Prevalance of <Emphasis Type="Italic">Chlamydia trochomatis</Emphasis>, <Emphasis Type="Italic">Ureaplasma urealyticum</Emphasis> and <Emphasis Type="Italic">Mycoplasma hominis</Emphasis> infections in the unexplained infertile women

Objective To prospectively investigate the prevalence of Chlamydia trachomatis (CT), Mycoplasma hominis (MH) and Ureaplasma urealyticum (UU) in the cervical canal and pouch of Douglas in unexplained infertile women and compare it to healthy controls in the Turkish population. Materials and methods A total of 31 women presenting with a history of infertility [n = 24 (77%) primary infertility, n = 7 (23%) secondary infertility] between 20 and 38 years of age and 31 women willing to have tubal ligation between 30 and 41 years of age were consecutively included into this study. Specimens were taken from intra-abdominal washings and from the cervical canal. CT, MH and UU were detected with polymerase chain reaction (PCR). Results Results of 62 women were analyzed. None of the participants met the criteria for salpingitis during laparoscopy. The most common infection in the cervical canal in both groups was UU, which was detected in 13 cases of infertile patients and 11 controls (P = 0.602). Cervical chlamydial and mycoplasmic infection was detected in one case each in infertile and control patients. Neither MH nor UU were obtained from the pouch of Douglas in both groups. Only CT was present in peritoneal fluid of an infertile woman who had also a concomitant chlamydial infection in the cervical canal. Conclusion Demonstration of cervical colonization of CT by PCR may be a promising method for the detection of asymptomatic pelvic infection in patients with unexplained infertility. However, screening for MH and UU is not cost-effective due to similar low rates of detection.     

Correlation between plasminogen activator inhibitor-1 (PAI-1) promoter 4G/5G polymorphism and metabolic/proinflammatory factors in polycystic ovary syndrome

Abstract

Polycystic Ovary Syndrome (PCOS) is the most common cause of subfertility associated to metabolic disorders. The aim of this study was to correlate metabolic and proinflammatory factors in women with PCOS. The frequency of Plasminogen Activator Inhibitor-1 (PAI-1) promoter 4?G/5?G polymorphism was also compared to healthy controls. We evaluated 79 PCOS and 79 healthy women. PAI-1 levels are positively correlated with proinflammatory factors in PCOS group. 4?G allele in PAI-1 gene was more frequent in PCOS and the 4G/4?G genotype was associated with increased PAI-1 levels. A correlation between insulin resistance and proinflammatory and overweight was also observed. C-reactive protein, serum levels of vascular cell adhesion molecule-1 (sVCAM-1), Lipid Accumulation Product (LAP) and vitamin D are good tools to evaluated factors associated to cardiovascular risk in women with PCOS.     

FSH-receptor <Emphasis Type="Italic">Ala307Thr</Emphasis> polymorphism is associated to polycystic ovary syndrome and to a higher responsiveness to exogenous FSH in Italian women

Objective  

Herein we analyzed FSH-R polymorphism at position 307 aiming (a) to assess the prevalence of the three allelic variants (Ala307Ala, Ala307Thr and Thr307Thr) in relation to the type of ovary and (b) to clarify if the allelic variant could influence the responsiveness to exogenous FSH.     

Genetic polymorphisms of <Emphasis Type="Italic">FSHR,CYP17, CYP1A1, CAPN10, INSR,SERPINE1</Emphasis> genes in adolescent girls with polycystic ovary syndrome

Background  Polycystic ovary syndrome (PCOS), whose genetic basis is not completely well understood, is the most common endocrine disorder in women and it typically develops during adolescence. The aim of this study is to investigate the possible association between single nucleotide polymorphisms (SNPs) of FSHR, CYP17, CYP1A1, CAPN10, INSR, SERPINE1 genes and PCOS in adolescent girls. Methods  DNA samples from forty-four adolescent girls with PCOS and 50 healthy controls were analyzed by PCR-RFLP and direct DNA sequencing to determine the genotypic frequency of 17 different polymorphic loci on the FSHR (A307T, N680S), CYP17 (−34 T/C), CYP1A1 (T6235C), CAPN10 (44, 43, 19, 63), INSR (exon 17 C/T), SERPINE1 (4G/5G) genes. Genotyping of exon 12 (six polymorphisms) and intron 12 (one polymorphism) of INSR gene by direct DNA sequencing was performed for the first time in this study. Results  No significant differences were observed in the genotype and allele distributions of above mentioned polymorphisms between cases and control groups. Conclusion  Our data does not support an association between SNPs of FSHR, CYP17, CYP1A1, CAPN10, INSR, SERPINE1 genes and susceptibility to PCOS or related traits in Turkish adolescent girls.     

Melanocortin 3 receptor gene polymorphism is associated with polycystic ovary syndrome in Turkish population

Polycystic ovary syndrome (PCOS) is a frequent complex disorder with an ill-defined etiology. Genetic factors seem rather effective at the occurrence of the disease, however, the evidence of established various studies results are unsatisfied. We aimed to make a contribution to the genetic baseline of the disease by investigating melanocortin 3 receptor gene polymorphism in affected patients. 101 PCOS patients and 162 age-matched healthy volunteered control subjects recruited to the study. PCOS patients classified according to their BMI class and insulin resistance situation. Anthropometric measurements, physical examination results, laboratory findings, and hormone levels were recorded for each participant and analysis of two SNPs on the MC3R gene; rs3746619 and rs3827103 were performed. Although no significant difference was observed in rs3827103 polymorphism between PCOS patients and controls; rs3746619 polymorphism was determined associated with PCOS in the heritage of dominant (AA + AC) and co-dominant (AA) genotypes. Two polymorphisms did not found related to obesity and insulin resistance in PCOS subgroups analysis. MC3R gene rs 3746619 polymorphism was found associated with PCOS in the Turkish population and may make a contribution to the genetic baseline of the disease.     

CYP1A1 polymorphism in adolescents with polycystic ovary syndrome

Objective

To evaluate the rates of the CYP1A1 Ile/Val polymorphism in Turkish adolescent females.

Methods

The CYP1A1 Ile/Val polymorphism was analyzed by collecting DNA samples from 44 adolescents with polycystic ovary syndrome (PCOS)—according to the Rotterdam criteria—and 120 healthy female controls aged 13-18 years in Ankara, Turkey.

Results

There was a 2.5-fold increase in the frequency of the CYP1A1 Ile/Val genotype in adolescents with PCOS compared with the control group (odds ratio [OR] 2.54; 95% confidence interval [CI], 1.143-5.637; P < 0.001), in addition to a 2.4-fold increase in the frequency of the Val allele (OR 2.43; 95% CI, 1.099-5.397; P < 0.001).

Conclusion

The data show an association between CYP1A1 and PCOS, indicating that variant alleles of the gene may affect the metabolic and transport pathway of estrogens, thus causing PCOS.     

Comparative Study of Biological and Technological Characters in Three Generations of Silkworm <Emphasis Type="Italic">Bombyx</Emphasis><Emphasis Type="Italic">mori</Emphasis> L. Ameiotic,Parthenogenetically Cloned Lines

Purpose: Detect any deviation in biologic and technologic characters of eight ameiotic-parthenogenetically cloned lines of Bombyx mori L. from different origins from a normal sexually reproduced control line in three generations.Methods: Comparative study of the three generations was conducted in SES, Vratza, unit of the National Center for Agrarian Sciences of Bulgaria after fixing all environmental rearing conditions.Results: The ameiotic-parthen-clones displayed good parthenogenetic development, although total hatchability was significantly less than the sexually reproducing control populations. Survival rates between clones and control were not significantly different. All clones displayed significantly longer larval periods. Slight decline in second generation, and a steeper one in the third generation were observed for all eight cloned lines in cocoon weight, shell weight, and shell ratio and these differences were statistically significant. Cocoon yield was significantly lower than the control throughout the three generations.Conclusions: Our parthen-cloning method has a high rate of success in comparison to other cloning methods, the cloned progeny populations although were weaker technologically (cocoon weight, shell weight, and shell ratio), the biological characters (parthenogenetic development and survival rate) were not compromised. Further study is needed to determine the thermal needs of the cloned embryos and metabolic rate of all stages.     

Length difference between equine <Emphasis Type="Italic">ZFX</Emphasis> and <Emphasis Type="Italic">ZFY</Emphasis> genes and its application for molecular sex determination

Purpose  

We analyzed the sex chromosome-encoding ZFX-ZFY genes and tested molecular sexing using the amplification patterns of intron 9 of ZFX-ZFY in the horse.     

PAI-1基因启动子区4G/5G基因多态性与多囊卵巢综合征

多囊卵巢综合征(polycystic ovary syndrome,PCOS)是育龄期女性最常见的生殖内分泌疾病,病因迄今不明,具有高度的家族聚集性,提示遗传因素在其发病中起重要作用。纤溶酶原激活物抑制剂1(plasminogen activator inhibitor-1,PAI-1)是纤溶系统的主要生理抑制剂,大量研究表明PAI-1基因启动子区4G/5G基因多态性可通过升高血浆PAI-1水平及活性影响胰岛素的敏感性,参与胰岛素抵抗(insulin resistance,IR)的形成。IR是PCOS主要的病理生理机制,与PCOS患者肥胖、自然流产等的发生密切相关,提示PAI-1基因启动子区4G/5G基因多态性与PCOS的发生、发展可能有着密切的关系。因此,PAI-1基因启动子区4G/5G基因多态性与PCOS的相关研究也成为近年研究热点,主要涉及PCOS的发病、肥胖、IR、自然流产及远期并发心血管疾病等,但相关结论尚存争议。     

<Emphasis Type="Italic">FTO</Emphasis>, <Emphasis Type="Italic">GCKR</Emphasis>, <Emphasis Type="Italic">CDKAL1</Emphasis> and <Emphasis Type="Italic">CDKN2A/B</Emphasis> gene polymorphisms and the risk of gestational diabetes mellitus: a meta-analysis

Purpose

Studies had examined the associations between genetic polymorphisms and the risk of gestational diabetes mellitus (GDM). However, conclusions of these studies were controversial due to the smaller sample size and limited statistical power. We carried out a meta-analysis with the aim of providing a more comprehensive summary of the currently available research to evaluate the relationship between FTO, GCKR, CDKAL1 and CDKN2A/B gene polymorphisms and GDM risk.

Methods

Literature search was carried out in the PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure and Wangfang databases up to November 2017. Data were extracted by two independent reviewers and statistical analyses were performed with STATA software. Pooled odds ratios and 95% confidence intervals were calculated by Z test to assess the association between genetic polymorphisms and GDM risk. Stratified analysis was performed based on ethnicity. Heterogeneity and publication bias between studies were evaluated by Cochran’s Q test and Egger regression test, respectively.

Results

14 eligible studies were included. CDKAL1 rs7754840 and rs7756992 showed significant correlation with GDM risk under the allele, recessive, dominant, homozygote and heterozygote models. GCKR rs780094 and CDKN2A/B rs10811661 also showed the same association under the allele, recessive and heterozygote models. No associations between FTO rs9939609 and rs8050136, GCKR rs1260326 and GDM risk were found.

Conclusions

Our meta-analysis showed that two SNPs in particular(rs7754840 and rs7756992 in CDKAL1) were very strongly associated with GDM risk. GCKR rs780094 and CDKN2A/B rs10811661 polymorphisms were moderately associated with GDM risk.

     

Apolipoprotein E gene polymorphism and polycystic ovary syndrome patients in Western Anatolia, Turkey

Purpose  Dyslipidemia, cardiovascular disease and hypertension are more frequently seen in patients with PCOS than in normal patients. We aimed at evaluating the distribution of Apo E alleles that can influence cardiovascular risk of the PCOS patients and control subjects. Methods  In this study, 129 young women with PCOS and 91 healthy women were included. In all subjects we performed hormonal, biochemical and Apo E genetic analysis. Results  The Apo E3 allele was found at a significantly higher frequency in the PCOS patient group compared with the control group. The Apo E2 allele was found at a significantly higher frequency in the control group compared with the patient group with PCOS. Conclusions  Although there were genotype and allele differences between control and patient groups in this study, no statistically significant change was determined in lipid and other cardiovascular risk factors in connection with allele and genotype.     

<Emphasis Type="Italic">Salmonella</Emphasis> Mississippi: a rare cause of second trimester miscarriage

We report a case of transplacental transmission of Salmonella Mississippi resulting in a spontaneous miscarriage at 18 weeks gestation. The miscarriage occurred 1 week after resolution of an acute diarrheal illness. We recommend evaluation by stool culture for Salmonella infection in pregnant women with diarrheal illness.     

Association study of <Emphasis Type="Italic">HNF1A</Emphasis> in women with polycystic ovary syndrome

Purpose

This study aims to ascertain whether an association exists between hepatocyte nuclear factor 1 alpha (HNF1A) and polycystic ovary syndrome (PCOS).

Methods

One thousand one hundred thirty-eight PCOS and 1125 healthy control Han Chinese women were recruited from Reproductive Hospital Affiliated to Shandong University. Serum hormone, blood lipid level, and genomic DNA were obtained from the peripheral blood for this research. Two single-nucleotide polymorphisms (SNPs)—rs2393791 and rs7305618—located in HNF1A were genotyped using the Sequenom MassARRAY system.

Results

The allele frequencies of SNP rs7305618 had significant differences between PCOS patients and controls after adjusting for age and BMI (p = 0.023). Besides, PCOS patients carrying the rs7305618 CC genotype shown a higher testosterone level than the patients with CT + TT genotypes after being adjusted by age and BMI (p = 0.019).

Conclusions

A SNP located in the HNF1A gene is associated with PCOS among Han Chinese women. This suggested that variations in HNF1A might confer risk for PCOS.

     

A common interleukin-6 gene promoter polymorphism influences the clinical characteristics of women with polycystic ovary syndrome

OBJECTIVE: To investigate the association of a common polymorphism of the interleukin-6 gene (IL6) promoter with the occurence and the clinical characteristics of polycystic ovary syndrome (PCOS). DESIGN: Prospective, case-control study. SETTING: Academic research institution. PATIENT(S): Sixty-two patients with PCOS and 94 healthy controls. INTERVENTION(S): Peripheral venous puncture, ultrasonography, oral glucose tolerance test (OGTT), questionnaire. MAIN OUTCOME MEASURE(S): Genotype analysis with respect to the common -174 G/C polymorphism of the IL6 gene promoter, analysis of testosterone (T), androstendione, and sex hormone binding globulin serum levels, and evaluation of the OGTT. RESULT(S): Allele frequencies among women with PCOS and controls were 62.9% and 64.4%, respectively, for the wild-type G allele, and 37.1% and 35.6%, respectively, for the mutant C allele. We ascertained a significant association between presence of at least one mutant C allele and the clinical characteristics of affected women: these women were more likely to present with a body mass index >27 kg/m(2), elevated total T serum levels, and a pathological OGTT result. CONCLUSION(S): A common polymorphism of the IL6 promoter, although not associated with the presence of PCOS, is associated with the clinical characteristics of women affected by this condition.     

Tissue plasminogen activator and plasminogen activator inhibitor 1 in obese and lean patients with polycystic ovary syndrome

Objective. Disturbances in the fibrinolytic system are predictors of future cardiovascular events. The aim of this study was to compare plasminogen activator inhibitor 1 (PAI-1) activity and tissue plasminogen activator (tPA) mass concentration between patients with polycystic ovary syndrome (PCOS) and control subjects.

Design. One hundred thirty-five patients with PCOS (lean and obese) and 81 healthy controls were recruited for the study. Blood samples for PAI-1 activity and tPA mass were collected together with anthropometric measures.

Results. Obese patients with PCOS displayed increased tPA mass concentration in comparison with controls (p?<0.05), and this finding was consistent regardless of whether patients displayed signs of hyperandrogenism or not. When hyperandrogenism was introduced as a prerequisite for the PCOS diagnosis, obese patients with PCOS displayed increased PAI-1 activity as well, p?<0.05. Lean patients with PCOS did not differ in terms of PAI-1 activity or tPA mass concentration in comparison to controls.

Conclusion. Obese women with PCOS have impaired fibrinolysis, in particular if they also display objective biochemical markers of hyperandrogenism.     

No association of <Emphasis Type="Italic">TAP1</Emphasis> and <Emphasis Type="Italic">TAP2</Emphasis> genes polymorphism with risk of cervical cancer in north Indian population

Background  Transporter associated with antigen processing (TAP), a member of the ATP-binding cassette transporter super family, is composed of two integral membrane proteins, TAP-1 and TAP-2. The TAP gene product is involved in the processing of endogenous peptides that bind to MHC class I molecules. Mutations and/or polymorphism within these genes could alter the efficacy of the immune response which might be relevant for the development of autoimmune diseases and cancer. Methods  DNA was isolated from peripheral blood sample of 200 patients with cervical cancer and 200 healthy controls. TAP1 and TAP2 allele polymorphism were determined by polymerase chain reaction. Result  Significant protective OR (OR = 0.22 95% CI = 0.09–0.51, P < 0.001-OR = 0.47, 95% CI = 0.24–0.92, P = 0.02) was observed for GG and combined AG+GG genotypes of TAP2 in patients with SCC respectively. Similarly, such genotypes (GG, AG+GG) appeared same OR for patient with cervical cancer in study group (OR = 0.12, 95% CI = 0.04–0.39-P < 0.001-OR = 0.5 ,95% CI = 0.25–0.95-P = 0.03). There was decrease risk of cervical cancer in user of oral contraceptive with AG and GG genotypes of TAP2 (OR = 0.55, 95% Cl = 0.41–0.73, P = 0.002, OR = 0.09, 95% CI = 0.02–0.36, P < 0.001) respectively. In case of TAP1 gene all allelic polymorphisms showed a decrease OR in patients with cervical cancer in passive smokers and user of oral contraceptives, though, no significant Conclusion  Thus, TAP1 and TAP2 genes polymorphism are not linked to cervical carcinoma, since no association was found between a particular genotype and the disease.     

Association of <Emphasis Type="Italic">TUSC1</Emphasis> and <Emphasis Type="Italic">DPF3</Emphasis> gene polymorphisms with male infertility

Purpose

Recently, genome-wide association studies of a Hutterite population in the USA revealed that five single nucleotide polymorphisms (SNPs) with a significant association with sperm quality and/or function in ethnically diverse men from Chicago were significantly correlated with family size. Of these, three SNPs (rs7867029, rs7174015, and rs12870438) were found to be significantly associated with the risk of azoospermia and/or oligozoospermia in a Japanese population. In this study, we investigated whether the rs10966811 (located in an intergenic region between the TUSC1 and IZUMO3 genes) and rs10129954 (located in the DPF3 gene) SNPs, previously related to family size, are associated with male infertility. In addition, we performed association analysis between rs12348 in TUSC1 and rs2772579 in IZUMO3 and male infertility.

Methods

We genotyped 145 patients with infertility (including 83 patients with azoospermia and 62 with oligozoospermia) and 713 fertile controls by PCR-RFLP technique for polymorphism. Because rs10966811 has no restriction sites, the SNP rs12376894 with strong linkage disequilibrium was selected as an alternative to rs10966811.

Results

There was a statistically significant association between rs12376894 proxy SNP of rs10966811 and oligozoospermia. Also, a statistically significant association between rs10129954 and azoospermia, and oligozoospermia was observed. When we assessed the relationship between rs12348 in TUSC1 and rs2772579 in IZUMO3 and male infertility traits, we found that rs12348 in TUSC1 was significantly associated with azoospermia and oligozoospermia, but rs2772579 in IZUMO3 was not associated with male infertility.

Conclusion

We found that the polymorphisms in TUSC1 and DPF3 displayed strong associations with male infertility.