Epigenetic association analysis of clinical sub-phenotypes in patients with polycystic ovary syndrome (PCOS)
0
Citation
0
Reference
10
Related Paper
Abstract:
Polycystic ovarian syndrome (PCOS) is a complex disorder affecting up to 15–20% of reproductive women. PCOS has recently been investigated using genome-wide association studies revealing important mutations and DNA methylation sites associated with the syndrome. As a clinically highly heterogenous condition, studying the molecular basis of the differential manifestation of PCOS is both meaningful concerning individualized management and important for understanding the biology of PCOS. Using genome-wide DNA methylation data collected from PCOS patients, we performed a powerful region-based analysis to detect differentially methylated regions (DMR) by correlating DNA methylation pattern in a genomic region with the level of each PCOS clinical sub-phenotype. We identified seven significant DMRs on chromosome 19 (12877188-12876846 bp) and chromosome 6 (MHC region) associated with prolactin level, as well as chromosomes 11 and 2 associated with metabolic attributes. Functional annotation linked significant DNA methylation patterns to functional genes (HOOK2, BDNFl, HLA-G, HLA-H, HLA-J, RNF39, etc) of metabolic disorders and immunity or novel associations to serve as targets for validation and replication.Keywords:
Association (psychology)
Genetic Association
SUMMARY OBJECTIVE: Polycystic ovary syndrome can be divided into different subtypes, including insulin resistance and hyperandrogenism. The aim of this study was to investigate the relationship between serum asprosin levels and polycystic ovary syndrome subtypes. METHODS: A total of 93 women with polycystic ovary syndrome and 77 healthy women as controls were selected for this study. The clinical and laboratory data were compared between the Polycystic ovary syndrome group and the control group. The Polycystic ovary syndrome group was further divided into subgroups: (1) women with or without hyperandrogenism (polycystic ovary syndrome hyperandrogenism and Polycystic ovary syndrome none-hyperandrogenism, respectively) and (2) women with or without insulin resistance (polycystic ovary syndrome insulin resistance and Polycystic ovary syndrome none-insulin resistance, respectively). Serum asprosin was measured by using enenzyme-linked immunosorbent assay. RESULTS: Serum asprosin levels showed no significant difference between the polycystic ovary syndrome and control groups. However, it was significantly lower in the Polycystic ovary syndrome HA and insulin resistance groups compared with the respective Polycystic ovary syndrome none-hyperandrogenism and none-insulin resistance groups (p<0.05). In the Polycystic ovary syndrome group, serum asprosin was negatively correlated with body mass index, luteinizing hormone, testosterone, basal antral follicles, fasting insulin, homeostatic model assessment of insulin resistance, and triglycerides. After adjusting for body mass index, the correlations were not significant, and asprosin was only positively correlated with prolactin (prolactin; r=0.426, p<0.001). CONCLUSION: Our study shows that women with polycystic ovary syndrome hyperandrogenism or insulin resistance exhibit significantly lower serum asprosin levels compared with controls, and the lower asprosin level directly correlated with prolactin level.
Hyperandrogenism
Cite
Citations (8)
Objective To investigate the features of obesity and insulin resistance in polycystic ovary syndrome patients,and to analyze the relation of these clinical parameters to biochemical features.Methods Two hundred and seventy-six polycystic ovary syndrome patients were divided into obese group and no-obese group.The level of blood sugar and insulin,area under curve of insulin,the length of menses were compared between obese group and no-obese group.The relation of area under curve of insulin to biochemical features was analyzed.Results(1) Insulin resistance and the impaired glucose tolerance were not always congruity.(2) Compared with polycystic ovary syndrome patients without obese,the rate of insulin resistance was significantly higher in obese polycystic ovary syndrome patients(P0.05),and the length of menses was longer in obese polycystic ovary syndrome patients.(3) Insulin area under the curve was positively correlated with BMI and T,negatively correlated with ratio of LH/FSH.Conclusion Insulin resistance is common in polycystic ovary syndrome patients.Compared with polycystic ovary syndrome patients without obese,the rate of insulin resistance is significantly higher in obese group(P0.05).Obesity is an important risk factor for polycystic ovary syndrome patients,and it can aggravate the clinical signs of polycystic ovary syndrome.
Cite
Citations (0)
Androgen Excess
Cite
Citations (5)
Reproductive system
Cite
Citations (21)
Hyperinsulinemia
Hyperandrogenism
Cite
Citations (104)
Purpose of review As the prevalence of pediatric obesity escalates, polycystic ovary syndrome is an increasingly common morbidity for adolescent females. This review describes recent insights into the pathophysiology and treatment of polycystic ovary syndrome, with special attention given to the relationship between polycystic ovary syndrome and obesity. Recent findings Recent research has elucidated three key concepts in our understanding of polycystic ovary syndrome. First, patients may enter the hyperandrogenism–hyperinsulinism cycle of polycystic ovary syndrome via several pathways, including genetic polymorphisms that affect androgen synthesis, fetal programming that alters lipid and glucose metabolism, and obesity accompanied by insulin resistance. Second, obesity plays a significant role in the pathophysiology of polycystic ovary syndrome by increasing free androgen concentrations through multiple mechanisms. Finally, just as the etiology of polycystic ovary syndrome is multifactorial, successful treatment will probably require a combination of lifestyle modification and therapeutic interventions. Summary Obesity contributes to the pathophysiology of polycystic ovary syndrome and increases the likelihood of associated metabolic and cardiovascular morbidities.
Hyperandrogenism
Androgen Excess
Cite
Citations (37)
Transgenerational epigenetics, the study of non-genetic transfer of information from one generation to the next, has gained much attention in the past few decades due to the fact that, in many instances, epigenetic processes outweigh direct genetic processes in the manifestation of aberrant phenotypes across several generations. Maternal effects, or the influences of maternal environment, phenotype, and/or genotype on offsprings' phenotypes, independently of the offsprings' genotypes, are a subcategory of transgenerational epigenetics. Due to the intimate role of the mother during early development in animals, there is much interest in investigating the means by which maternal effects can shape the individual. Maternal effects are responsible for cellular organization, determination of the body axis, initiation and maturation of organ systems, and physiological performance of a wide variety of species and biological systems. The cardiovascular system is the first to become functional and can significantly influence the development of other organ systems. Thus, it is important to elucidate the role of maternal effects in cardiovascular development, and to understand its impact on adult cardiovascular health. Topics to be addressed include: (1) how and when do maternal effects change the developmental trajectory of the cardiovascular system to permanently alter the adult's cardiovascular phenotype, (2) what molecular mechanisms have been associated with maternally induced cardiovascular phenotypes, and (3) what are the evolutionary implications of maternally mediated changes in cardiovascular phenotype?
Transgenerational epigenetics
Cardiovascular Health
Epigenesis
Maternal effect
Cite
Citations (26)
Abstract The outcome of epigenetic responses to stress depends strictly on genetic background, suggesting that altered phenotypes, when induced, are created by a combination of induced epigenetic factors and pre‐existing allelic ones. When individuals with altered phenotypes are selected and subjected to successive breeding, alleles that potentiate epigenetic responses could accumulate in offspring populations. It is reasonable to suppose that many, if not all, of these allelic genes could also be involved in creating new phenotypes under nonstressful conditions. In this review, I discuss the possibility that the accumulation of such alleles in selected individuals with an epigenetic phenotype could give rise to individuals that exhibit the same phenotype even in the absence of stress.
Cite
Citations (3)
The etiology and pathogenesis of polycystic ovary syndrome (PCOS) is still unknown. Using real-time PCR, we detected that polycystic ovaries showed almost ten times lower expression of ghrelin mRNA than normal ovaries, whereas the mRNA levels in blood cells were similar in both study groups. This suggests that the presence of ghrelin in PCOS and normal ovaries may have an autocrine/paracrine modulatory effect on ovary functions and local significance in the etiology of PCOS.
Etiology
Pathogenesis
Cite
Citations (14)
Polycystic ovary syndrome (PCOS) is a highly heterogeneous reproductive system disorder of which the aetiology is not fully understood. Previous association studies have been conducted on >100 candidate genes, which principally related to reproductive hormones, cellular metabolism and chronic inflammation. Heritable tendencies have long been recognized for pathogeneses of PCOS, and recently a genome-wide association study (GWAS) in PCOS provides new clues to understand the genetic components and pathways in PCOS physiology. However, the current knowledge of the pathogenesis of PCOS is still in its infancy. Further studies using new technologies such as next-generation sequencing (NGS) shall be useful to understand more causal variants for PCOS.
Genome-wide Association Study
Genetic Association
Candidate gene
Etiology
Androgen Excess
Cite
Citations (52)