scholarly journals Novel HumanMethylatyion450 Analyses Reveal DNA Methylation Predictors of Future Diabetes Onset in Women With Polycystic Ovarian Syndrome

Author(s):  
Mark Kitchen ◽  
Ayesha Manzur ◽  
Anthony Fryer ◽  
Pensee Wu

Abstract Aims. Polycystic ovarian syndrome (PCOS) is a common endocrine disorder characterised by ovarian morphological, systemic biochemical, and menstrual changes. Women with PCOS are at significantly increased risk of raised fasting glucose, impaired glucose tolerance, and diabetes. Recognition of these complications and early intervention are key to good health outcomes. We sought to identify DNA methylation patterns that may predict future diabetes onset in this high-risk PCOS population. Patients and Methods. Peripheral blood samples from women with PCOS and women with PCOS who later developed diabetes, were analysed by Illumina HumanMethylation450 BeadChip-arrays. Bisulphite-Pyrosequencing™ was used to validate and confirm array methylation data. Results. Array analyses identified 273 differentially methylated CpG loci (≥ 0.2 β-value change) at initial diagnosis of PCOS, between women who did or did not later develop diabetes. 19 of these sites demonstrated differential methylation in the same direction in ≥ five sample pairs. Methylation in three of the candidates (cg11897887, cg02819655, and cg25542007) showed the best concordance with corresponding array β-values, and, most clearly differentiated ‘cases’ from ‘controls’. Conclusions. We have identified novel methylation biomarkers that could predict future onset of diabetes in this high-risk population. Use of methylation analyses to identify women who are likely to develop diabetes at diagnosis of PCOS may facilitate timely lifestyle interventions to reduce future morbidity.

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Qun Yu ◽  
Jin-Bei Wang

Aim of Study. To assess status of thyroid function and thyroid disorders particularly subclinical hypothyroidism (SCH) in subjects with polycystic ovarian syndrome (PCOS) and impact of SCH on various clinical and biochemical parameters and cardiovascular risk in PCOS.Methods. Hundred females diagnosed with PCOS as per Rotterdam criteria and 100 normal controls were recruited and were subjected to elaborate anthropometric, clinical, and biochemical assessment.Results. Notable findings included significantly higher frequency of subjects with subclinical hypothyroidism (p=0.0002), autoimmune thyroiditis (p<0.001), and goitre (p=0.02) in polycystic ovarian syndrome subjects compared to control subjects. Further SCH PCOS subjects were found to harbor significantly higher HOMA-IR (p<0.05) and frequency of subjects with dyslipidemia (p<0.05) compared to both euthyroid PCOS and euthyroid control subjects. Though frequency of subjects with cardiovascular risk factors was higher in SCH PCOS group than euthyroid PCOS group, it failed to reach statistical significance.Conclusion. We concluded that PCOS is associated with high incidence of SCH and AIT compared to normal population and SCH poses increased risk of cardiovascular disorder in PCOS.


2021 ◽  
pp. 003693302110432
Author(s):  
Tazkia Mawaddatina ◽  
Uki Retno Budihastuti ◽  
Dwi Rahayu

Background and Aims Polycystic ovarian syndrome is a reproductive problem of women with high prevalence cases accompanied by obesity conditions. Obesity condition can be seen from the size of waist circumference, hip circumference, arm span, and waist-to-hip ratio. This study aims to find out the risk factors between waist circumference size, hip circumference, arm span, and waist-to-hip ratio with polycystic ovarian syndrome. Methods This research is an analytical observation using a case-control approach conducted at Sekar Fertility Clinic and Poly Obgyn Dr Moewardi General Hospital Surakarta. Subjects were 150 consisting of 75 polycystic ovarian syndrome women and 75 normal fertile women. Sampling techniques used in this study are purposive sampling, researchers doing anthropometric measurements in the form of waist circumference, hip circumference, arm span, and waist-to-hip ratio simultaneously. The results were analyzed using Statistic Product and Service Solution 25. Results The results of the study obtained waist circumference with polycystic ovarian syndrome ( b = 3.002; CI 95% = 3.41–123.5; p = 0.001), hip circumference ( b = −2.671; CI 95% = 0.01–0.37; p = 0.002), arm span ( b = 5.318; CI 95% = 32.23–129.58; p < 0.001) and waist-to-hip ratio ( b = 1.761; CI 95% = 1.02–33.01; p = 0.047). Conclusion Waist circumference size, hip circumference, arm span, and waist-to-hip ratio correlate to a high risk of polycystic ovarian syndrome. Arm span is more dominant as an indicator of high risk to polycystic ovarian syndrome compared to waist circumference, hip circumference, and waist-to-hip ratio.


BMC Medicine ◽  
2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Biyuan Luo ◽  
Fang Ma ◽  
Hao Liu ◽  
Jixiong Hu ◽  
Le Rao ◽  
...  

Abstract Background Aberrant DNA methylation may offer opportunities in revolutionizing cancer screening and diagnosis. We sought to identify a non-invasive DNA methylation-based screening approach using cell-free DNA (cfDNA) for early detection of hepatocellular carcinoma (HCC). Methods Differentially, DNA methylation blocks were determined by comparing methylation profiles of biopsy-proven HCC, liver cirrhosis, and normal tissue samples with high throughput DNA bisulfite sequencing. A multi-layer HCC screening model was subsequently constructed based on tissue-derived differentially methylated blocks (DMBs). This model was tested in a cohort consisting of 120 HCC, 92 liver cirrhotic, and 290 healthy plasma samples including 65 hepatitis B surface antigen-seropositive (HBsAg+) samples, independently validated in a cohort consisting of 67 HCC, 111 liver cirrhotic, and 242 healthy plasma samples including 56 HBsAg+ samples. Results Based on methylation profiling of tissue samples, 2321 DMBs were identified, which were subsequently used to construct a cfDNA-based HCC screening model, achieved a sensitivity of 86% and specificity of 98% in the training cohort and a sensitivity of 84% and specificity of 96% in the independent validation cohort. This model obtained a sensitivity of 76% in 37 early-stage HCC (Barcelona clinical liver cancer [BCLC] stage 0-A) patients. The screening model can effectively discriminate HCC patients from non-HCC controls, including liver cirrhotic patients, asymptomatic HBsAg+ and healthy individuals, achieving an AUC of 0.957(95% CI 0.939–0.975), whereas serum α-fetoprotein (AFP) only achieved an AUC of 0.803 (95% CI 0.758–0.847). Besides detecting patients with early-stage HCC from non-HCC controls, this model showed high capacity for distinguishing early-stage HCC from a high risk population (AUC=0.934; 95% CI 0.905–0.963), also significantly outperforming AFP. Furthermore, our model also showed superior performance in distinguishing HCC with normal AFP (< 20ng ml−1) from high risk population (AUC=0.93; 95% CI 0.892–0.969). Conclusions We have developed a sensitive blood-based non-invasive HCC screening model which can effectively distinguish early-stage HCC patients from high risk population and demonstrated its performance through an independent validation cohort. Trial registration The study was approved by the ethic committee of The Second Xiangya Hospital of Central South University (KYLL2018072) and Chongqing University Cancer Hospital (2019167). The study is registered at ClinicalTrials.gov(#NCT04383353).


2019 ◽  
Vol 3 (5) ◽  

The Polycystic ovarian syndrome affects 6-15 % of reproductive age women worldwide. And recently the changing life styles and rising obesity worldwide have contributed to a rise in the incidence of PCOS. Though there are many issues with PCOS post conception. PCOS women are at increased risk of early pregnancy loss which is approx. three fold as compared to the women without PCOS. After successfully crossing the first trimester, they are at risk of developing pre- eclampsia, GDM, preterm birth and birth of small for gestational age infant. Also higher incidence of multiple pregnancies is there and the risks associated with them. All these leading to higher rate of c -section delivery. So, proper understanding of these risks, informing and counseling the patients regarding them facilitate closer maternal and fetal surveillance and help improving the outcome of pregnancy.


2021 ◽  
Author(s):  
Filip Ottosson ◽  
Einar Smith ◽  
Ulrika Ericson ◽  
Salvatore Di Somma ◽  
Paola Antonini ◽  
...  

Background Obesity is a key risk factor for type 2 diabetes, however, up to 20% of patients are normal weight. Our aim was to identify metabolite patterns reproducibly predictive of BMI, and subsequently to test if lean individuals who carry an obese metabolome are at hidden high risk of obesity related diseases, such as diabetes. Methods We measured 109 metabolites in fasted plasma samples of 7663 individuals from two Swedish and one Italian population-based cohort. Ridge regression models were used to predict BMI using the plasma metabolites. Individuals with a predicted BMI either more than 5 kg/m2 higher (overestimated) or lower (underestimated) than their actual BMI were characterized as outliers and further investigated for obesity related risk factors and future risk of diabetes and mortality. Results The plasma metabolome could predict BMI in all cohorts (r2 = 0.48, 0.26 and 0.19). The overestimated group had a BMI similar to individuals correctly predicted as normal weight, similar waist circumference, were not more likely to change weight over time but had a 2 times higher risk of future diabetes and an 80 % increased risk of all-cause mortality. These associations remained after adjustments for obesity-related risk factors and lifestyle parameters. Conclusions We found that lean individuals with an obese metabolome, have an increased risk for diabetes and all-cause mortality compared to lean individuals with a healthy metabolome. Metabolomics may be used to identify hidden high-risk individuals, in order to initiate lifestyle and pharmacological interventions.


2020 ◽  
Vol 66 (2) ◽  
pp. 123-137 ◽  
Author(s):  
Zhanrui Mao ◽  
Ting Li ◽  
Hui Zhao ◽  
Yulan Qin ◽  
Xuesong Wang ◽  
...  

2020 ◽  
pp. injuryprev-2019-043479 ◽  
Author(s):  
Veronica A Pear ◽  
Christopher D McCort ◽  
Yueju Li ◽  
Laurel Beckett ◽  
Daniel Tancredi ◽  
...  

BackgroundA substantial proportion of individuals who lawfully purchase firearms later become unlawful owners ('prohibited firearm owners'), usually following events associated with an increased risk for future violence. This high-risk population has not previously been described. We aimed to characterise all individuals in California's Armed and Prohibited Persons System (APPS), a statewide programme for recovering firearms from individuals who legally purchased them and later became prohibited from ownership.MethodsWe used univariate and bivariate statistics to describe and compare prohibited firearm owners in APPS with a random sample of non-prohibited firearm owners in relation to age, sex, race/ethnicity and type of firearms owned as of 1 February 2015. We also characterised the geographical distribution of prohibited firearm owners and described their prohibitions.ResultsOf the 18 976 prohibited firearm owners, most were men (93%), half were white (53%) and the mean age was 47 years. Prohibited firearm owners were more likely to be male and to be black or Hispanic people than non-prohibited owners. Both prohibited and non-prohibited firearm owners had an average of 2.6 firearms, mostly handguns. Nearly half (48%) of prohibited firearm owners had a felony conviction. Extrapolating from our findings, we estimated that there are approximately 100 000 persons in the USA who unlawfully maintained ownership of their firearms following a felony conviction.ConclusionsRetention of firearms among persons who become lawfully prohibited from possessing them is common in California. Given the nationwide dearth of a programme to recover such weapons, this is likely true in other states as well.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Christopher thiam seong Lim ◽  
Yun Jin Ong ◽  
Shao Wei Yong ◽  
Wee Ven Hing [email protected] ◽  
Mohammad Zulkarnain Bidin ◽  
...  

Abstract Background and Aims Pregnancy in chronic kidney disease (CKD) is associated with increased risk of adverse maternal outcomes and fetal outcomes. The risks are noticeable even in early stages of CKD. Despite the rising concern, there are few follow-up studies in this high-risk group. Method We followed up and analysed 538 pregnancies in 173 women with pre-existing of primary renal disease who were seen at a tertiary nephrology centre from January 2007 until December 2015. We sought to investigate the changes in laboratory and clinical parameters, maternal and fetal outcomes. Results Figure 1 showed the changes of parameters intra and post-partum period. Increase in weight (p=0.034, OR 1.135, 95% CI 1.01-1.276), antibiotics consumption (p=0.022, OR 0.088, 95% CI 0.011-0.0703), pregnancy-related hypertension (p=0.056, OR 0.161, 95% CI 0.025-1.05) and gromerulonephritis (p=0.049, OR 14.22, 95% CI 1.009- 200.52) were associated with worsening of proteinuria intra-pregnancy and post-pregnancy period. Age more than 30-year-old (p=0.024, OR 0.644, 95% CI 0.439-0.945), multiple pregnancies (p = 0.032, OR 14.4, 95% CI 1.25-165 , antibiotics usage (p=0.033, OR 27.59, 95% CI 1.302-585.169), diuretic usage (p=0.034, OR 0.003, 95% CI 1.26-0.646), pregnancy-related hypertension (p=0.06, OR 21.838, 95% CI 0.878-543.376) and proteinuria (&gt; 1.5g/d) (p=0.025, OR 0.235 95% CI 0.067-0.717) and fetal complications such as fetal death (p=0.013, OR 3.608 95% CI 1.311-9.930) was associated with rapid renal function decline of 25-50% . Elevation of serum uric acid is associated with a higher risk of adverse fetal outcome (r=0.845 p=0.004). Conclusion Multiple pregnancies, antibiotic usage, pregnancy-related hypertension are strong predictors of rapid maternal rapid function decline. Pre-conception counselling, minimization of antibiotic usage and aggressive blood pressure monitoring and treatment should be part of the standard treatment for this high-risk population.


2019 ◽  
Vol 34 (9) ◽  
pp. 1830-1837 ◽  
Author(s):  
Tomor Harnod ◽  
Weishan Chen ◽  
Jen-Hung Wang ◽  
Shinn-Zong Lin ◽  
Dah-Ching Ding

Abstract STUDY QUESTION Is polycystic ovarian syndrome (PCOS) in women associated with the increasing incidence of depression in an East Asian population? SUMMARY ANSWER Younger PCOS patients (aged 15–29 years), but not middle-aged patients, have an increased risk of depression in Taiwan. WHAT IS KNOWN ALREADY During reproductive age, 6–10% of women have PCOS. Among them, ~40% experience depression, mostly at young ages. STUDY DESIGN, SIZE, DURATION This is a retrospective population-based cohort study analysing depression risk in Taiwanese women using data from a nationwide database containing 1998–2013 data of nearly 1 million people. PARTICIPANTS/MATERIALS, SETTING, METHODS We included 15- to 50-year-old women newly diagnosed with PCOS during 1998–2013 from the Taiwan National Health Insurance Research Database as the PCOS cohort (n = 7684) and then randomly matched them 4 : 1 by sex, age and index year with women without PCOS as the comparison cohort (n = 30 736). We used multivariable Cox proportional hazard regression analysis to determine the association between PCOS and depression risk [hazard ratio (HR) with 95% confidence interval (CI)]. MAIN RESULTS AND THE ROLE OF CHANCE The incidence of depression was higher in the PCOS group than in the comparison group (6.67 vs. 4.82 per 1000 person-years; adjusted HR = 1.28, 95% CI = 1.12–1.46). PCOS patients aged 15–29 years had a significantly higher depression risk (adjusted HR = 1.39, 95% CI = 1.18–1.65); no such significant association was noted among patients aged 30–39 years and 40–50 years. LIMITATIONS, REASONS FOR CAUTION A history of malignancy, which may increase depression, could not be obtained for our study patients. Moreover, we could not obtain a family history of depression, a relevant risk factor for depression. Finally, the database has no records of body mass index, which may influence depression outcome. WIDER IMPLICATIONS OF THE FINDINGS In Taiwan, younger PCOS patients (15–29 years), but not the middle-aged patients, have an increased risk of depression. Our findings provide vital information to patients, clinicians, the Taiwan Government and other developing Asian countries to improve the PCOS treatment strategies in the future. Routine screening for depression in PCOS patients may be implemented into the health practice. STUDY FUNDING/COMPETING INTEREST(S) This study was supported in part by the Taiwan Ministry of Health and Welfare Clinical Trial Center (MOHW108-TDU-B-212-133 004), China Medical University Hospital, Academia Sinica Stroke Biosignature Project (BM10701010021), MOST Clinical Trial Consortium for Stroke (MOST 107-2321-B-039 -004-), Tseng-Lien Lin Foundation, Taichung, Taiwan and Katsuzo and Kiyo Aoshima Memorial Funds, Japan. No competing interest existed. TRIAL REGISTRATION NUMBER N/A.


2008 ◽  
Vol 193 (5) ◽  
pp. 378-382 ◽  
Author(s):  
Ian Kelleher ◽  
Michelle Harley ◽  
Fionnuala Lynch ◽  
Louise Arseneault ◽  
Carol Fitzpatrick ◽  
...  

BackgroundChildren and adolescents who report psychotic symptoms appear to be at increased risk for psychotic disorders in adulthood – a putative ‘symptomatic’ high-risk group. However, little research has investigated whether those in this high-risk population have increased rates of exposure to traumatic events in childhood, as seen in patients who have a psychotic illness.AimsTo examine whether adolescents with psychotic symptoms have an increased rate of traumatic experiences.MethodPsychiatric interviews were carried out with 211 adolescents aged between 12 and 15 years and their parents as part of a population-based study. The interview enquired about a number of early traumatic events including physical and sexual abuse, exposure to domestic violence and bullying.ResultsFourteen adolescents (6.6% of those interviewed) reported experiencing at least one psychotic symptom. Adolescents who reported psychotic symptoms were significantly more likely to have been physically abused in childhood, to have been exposed to domestic violence and to be identified as a bully/victim (that is, both a perpetrator and victim of bullying) than those who did not report such symptoms. These findings were not confounded by comorbid psychiatric illness or family history of psychiatric history.ConclusionsOur findings suggest that childhood trauma may increase the risk of psychotic experiences. The characteristics of bully/victims deserve further study.


Sign in / Sign up

Export Citation Format

Share Document