scholarly journals Alteration of serum leptin and LEP/LEPR promoter methylation in Prader-Willi syndrome

2021 ◽  
Author(s):  
Jelte Wieting ◽  
Kirsten Jahn ◽  
Vanessa Buchholz ◽  
Ralf Lichtinghagen ◽  
Stefan Bleich ◽  
...  
Keyword(s):  
Promoter Methylation ◽  
Chromosome Region ◽  
Neurodevelopmental Disorder ◽  
Methylation Status ◽  
Leptin Resistance ◽  
Mortality Factor ◽  
Enzyme Linked Immunosorbent Assay ◽  
Prader Willi Syndrome ◽  
Serum Leptin ◽  
Methylation Rate

Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder based on a loss of paternally expressed but maternally imprinted genes in chromosome region 15q11-13. During child development, PWS usually results in insatiable appetite with subsequent obesity representing the major mortality factor. The neurobiological basis of PWS-typical hyperphagia has remained poorly understood. Many PWS-typical abnormalities are based on hypothalamic dysregulation, the region in which hunger and satiety are hormonally regulated, with the hormone leptin being a main long-term regulator of satiety. Previous studies in PWS have inconsistently shown leptin alterations solely in early childhood, without investigating the leptin system on an epigenetic level. The present study investigates serum leptin levels (S-leptin) and methylation of the leptin (LEP) and leptin receptor gene (LEPR) promoter in 24 individuals with PWS compared to 13 healthy controls matched for sex, age, and body mass index (BMI) and relates the results to the extent of hyperphagia in PWS. S-Leptin levels were obtained by Enzyme-linked Immunosorbent Assay. LEP/LEPR-promoter methylation was assessed by DNA-bisulfite-sequencing, hyperphagia by Hyperphagia Questionnaire for Clinical Trials (HQ-CT). PWS and control groups differed significantly in S-leptin levels with higher S-leptin in PWS. Methylation analysis showed significant differences in mean promoter methylation rate both for LEP and LEPR with a lower methylation rate in PWS. LEPR, but not LEP methylation correlated with S-leptin levels. S-leptin and both LEP and LEPR methylation did not correlate with HQ-CT scores in PWS. The present study is the first to show significantly elevated S-leptin levels in an adult PWS cohort combined with an altered, downregulated LEP and LEPR promoter methylation status compared to BMI-matched controls. Analogous to previous studies, no link to the behavioral dimension could be drawn. Overall, the results suggest an increased leptin dysregulation in PWS, whereby the findings partly mirror leptin resistance seen in non-syndromic obesity.

scholarly journals The Value and Clinical Significance of ZNF582 gene Methylation in the Diagnosis of Cervical Cancer

2020 ◽  
Author(s):  
Chunhe Zhang ◽  
Shaowei Fu ◽  
Luyue Wang ◽  
Fang Wang ◽  
Dan Wu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Mrna Expression ◽  
Promoter Methylation ◽  
Zinc Finger Protein ◽  
Methylation Status ◽  
Cervical Lesions ◽  
Gene Methylation ◽  
Methylation Rate ◽  
Specificity And Sensitivity ◽  
Cancer Tissues

Abstract Background This study aimed to determine whether ZNF582 gene methylation and tissue protein expression can be used as a tool with high sensitivity and specificity for cervical cancer screening. We analyzed the correlation between promoter methylation of the zinc finger protein 582 (ZNF582) gene and cervical cancer and high risk HPV16/18 infection. Methods Tissue samples of normal cervical or chronic cervicitis (n=51), CIN (cervical intraepithelial neoplasia) (n=35), and cervical carcinoma (n=68) were tested for HPV16/18 infection by polymerase chain reaction (PCR). We also detected the methylation status of the ZNF582 gene promoter in the same tissues by methylation specific PCR (MSP), then analyzed the correlation between ZNF582 promoter methylation and HPV16/18 infection. Immunohistochemistry was used to analyze ZNF582 gene expression in 152 cervical tissues. We detected ZNF582 mRNA expression in cervical tissues (including cancer and non-cancer) by real-time fluorescence quantitative PCR (qRT-PCR).Results Among 93 high grade cervical lesions (CINII and above) and cervical cancer samples, 57 cases were positive for HPV16/18 infection and 36 cases were negative. ZNF582 gene methylation occurred in 9 out of 51 cases in normal cervical tissues (17.6%), 16 of 35 cases in CIN tissues (45.7%), and 50 of 68 cases in cervical cancer (73.5%). The differences in methylation rate of the three groups were statistically significant (P<0.05). The ZNF582 methylation rate in the positive HPV16/18 infection group was 73.7%, while the negative group was 63.9%. Compared with normal tissues, ZNF582 protein was highly expressed in cervical cancer tissues, but mRNA expression was low.Conclusion While ZNF582 protein is highly expressed in cervical cancer tissues, it was not sufficient for use as a standard for cervical cancer staging. On the other hand, ZNF582 promoter methylation had high specificity and sensitivity in detecting CINII and highly diseased cervical lesions and could be used as a diagnostic marker for cervical cancer of women.

scholarly journals Serum Leptin Concentration is Correlated to Insulin Resistance in Polycystic Ovary Syndrome (PCOS) Patients

2021 ◽  
Vol 5 (2) ◽  
pp. 93
Author(s):  
Arsyi Adliah Anwar ◽  
Nusratuddin Abdullah ◽  
Andi Nursanty Padjalangi ◽  
Firdaus Hamid ◽  
Nasrudin Andi Mappeware ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Ovarian Function ◽  
Polycystic Ovary ◽  
Leptin Resistance ◽  
Enzyme Linked Immunosorbent Assay ◽  
Strong Positive Correlation ◽  
Model Assessment ◽  
Ovary Syndrome ◽  
Serum Leptin

Background: Leptin resistance which leads to excessive circulating leptin levels is thought to affect ovarian function. This study aimed to study the correlation between serum leptin levels with insulin resistance in patients with polycystic ovary syndrome.Materials and Methods: This cross-sectional study was undertaken in several teaching hospitals in Makassar, Indonesia. We included patients diagnosed with polycystic ovary syndrome (PCOS) aged 18-40 years old. Serum leptin levels were examined in all eligible subjects using the enzyme-linked immunosorbent assay (ELISA) method. The results obtained were further analyzed statistically.Results: Approximately 53 PCOS subjects were included in this study, 25 subjects with insulin resistance and 28 subjects without insulin resistance. After examining serum leptin levels, we found that leptin is directly proportional to insulin resistance (p<0.001). We even found a strong positive correlation between serum leptin levels with homeostatic model assessment for insulin resistance (HOMA-IR) levels (r=0.659; p<0.001). Leptin was found to be independent of HOMA-IR, not influenced by confounding factors such as body mass index (BMI) (p=0.090).Conclusion: There was a significant correlation between serum leptin levels and HOMA-IR values in PCOS patients. This correlation was found to be significant regardless of patient's BMI, therefore is considered to have a direct effect on insulin resistance in PCOS.Keywords: polycystic ovary syndrome, leptin, insulin resistance, HOMA-IR

POSTOPERATIVE COMPLIANCE OF BARIATRIC SURGERY PATIENTS REGARDING THE ASSESSMENT OF SERUM LEPTIN LEVELS AND INSULIN RESISTANCE

2019 ◽  
Vol 49 (1/2019) ◽  
Keyword(s):  
Insulin Resistance ◽  
Bariatric Surgery ◽  
Serum Levels ◽  
Medical Laboratory ◽  
Leptin Resistance ◽  
Obese Patients ◽  
Laboratory Assessment ◽  
Serum Leptin ◽  
Before And After ◽  
Bariatric Patients

Background and aims: Overweight and obese patients who undergo bariatric surgery require a rigorous clinical and paraclinical assessment both before and after the surgery at 3, 6, and 12 months.The present study aims the assessment of serum leptin levels and insulin resistance status in compliant bariatric patients to scheduled medical laboratory assessment at 6 months after surgery. Material and Method: The study included 109 eligible patients selected for bariatric surgery, 48 of whom attended the scheduled visit at 6 months after the surgery. Laboratory assessing regarded the insulin resistance by determining before meal the serum levels of leptin, glucose and insulin, as well as HOMA 1 and HOMA 2 indexes. Results: Patients who underwent bariatric treatment experienced a significant decrease in insulin resistance status. A higher percentage in the preoperative group was recorded in women, feature which was also recorded in the postoperative group that attended the scheduled visit at 6 months after surgery. Age is also an important factor that significantly influences the behavioral adherence to postoperative visits. Conclusions: Insulin resistance status improved significantly in 6 months after bariatric surgery among the fully compliant patients. The percentage of attendance at scheduled visits is higher among women, and decreases with age. Keywords: obesity surgery, leptin resistance, insulin resistance, HOMA index, compliance

A Case Of Prader-Willi Syndrome With Behavioural Disturbances: A Successful Multidisciplinary Management Approach

2020 ◽  
Vol 5 (1) ◽  
pp. 83
Author(s):  
Nor Jannah Nasution Raduan ◽  
Mohd Razali Salleh ◽  
Norharlina Bahar ◽  
Mohd Faiz Md Tahir ◽  
Najwa Hanim Md Rosli
Keyword(s):  
Neurodevelopmental Disorder ◽  
Pressure Control ◽  
Family Therapist ◽  
Sleep Apnoea ◽  
Obstructive Sleep Apnoea Syndrome ◽  
Management Approach ◽  
Adolescent Psychiatrist ◽  
Prader Willi Syndrome ◽  
Obstructive Sleep ◽  
Genetically Determined

Prader-Willi Syndrome (PWS) is a genetically determined neurodevelopmental disorder occurring in 1 in 15,000 births. PWS is a rare case in Malaysia and a successful approach to its management has not been well reported here. We present a case of a 13-year-old boy with Prader-Willi Syndrome with prominent behavioural disturbances characterised by temper tantrums, compulsive food intake, stubbornness, stealing and impulsivity further complicated by underlying morbid obesity, poorly controlled type 2 diabetes mellitus, hypertension, dyslipidaemia, obstructive sleep apnoea syndrome and intellectual disability. Multidisciplinary approach involving child and adolescent psychiatrist, occupational therapist, counsellor, family therapist, endocrinologist and dietician has shown to improve the patient’s weight, glucose and blood pressure control and most importantly the behavioural disturbances.

scholarly journals Genome-wide analysis identifies critical DNA methylations within NTRKs genes in colorectal cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Zijian Chen ◽  
Zenghong Huang ◽  
Yanxin Luo ◽  
Qi Zou ◽  
Liangliang Bai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Promoter Methylation ◽  
Expression Profiles ◽  
Methylation Status ◽  
Gene Promoter ◽  
Normal Mucosa ◽  
Suppressor Gene ◽  
Survival Outcome ◽  
Prognostic Models

Abstract Background Neurotrophic tropomyosin receptor kinases (NTRKs) are a gene family function as oncogene or tumor suppressor gene in distinct cancers. We aimed to investigate the methylation and expression profiles and prognostic value of NTRKs gene in colorectal cancer (CRC). Methods An analysis of DNA methylation and expression profiles in CRC patients was performed to explore the critical methylations within NTRKs genes. The methylation marker was validated in a retrospectively collected cohort of 229 CRC patients and tested in other tumor types from TCGA. DNA methylation status was determined by quantitative methylation-specific PCR (QMSP). Results The profiles in six CRC cohorts showed that NTRKs gene promoter was more frequently methylated in CRC compared to normal mucosa, which was associated with suppressed gene expression. We identified a specific methylated region within NTRK3 promoter targeted by cg27034819 and cg11525479 that best predicted survival outcome in CRC. NTRK3 promoter methylation showed independently predictive value for survival outcome in the validation cohort (P = 0.004, HR 2.688, 95% CI [1.355, 5.333]). Based on this, a nomogram predicting survival outcome was developed with a C-index of 0.705. Furthermore, the addition of NTRK3 promoter methylation improved the performance of currently-used prognostic model (AIC: 516.49 vs 513.91; LR: 39.06 vs 43.64, P = 0.032). Finally, NTRK3 promoter methylation also predicted survival in other tumors, including pancreatic cancer, glioblastoma and stomach adenocarcinoma. Conclusions This study highlights the essential value of NTRK3 methylation in prognostic evaluation and the potential to improve current prognostic models in CRC and other tumors.

Association Between Cyclin D1 Polymorphism with CpG Island Promoter Methylation Status of Tumor Suppressor Genes in Gastric Cancer

2010 ◽  
Vol 55 (12) ◽  
pp. 3449-3457 ◽  
Author(s):  
Tomomitsu Tahara ◽  
Tomoyuki Shibata ◽  
Masakatsu Nakamura ◽  
Hiromi Yamashita ◽  
Daisuke Yoshioka ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Suppressor ◽  
Cyclin D1 ◽  
Promoter Methylation ◽  
Tumor Suppressor Genes ◽  
Cpg Island ◽  
Methylation Status ◽  
Suppressor Genes ◽  
Promoter Methylation Status

scholarly journals Time for a general approval of growth hormone treatment in adults with Prader–Willi syndrome

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Charlotte Höybye ◽  
◽  
Anthony J. Holland ◽  
Daniel J. Driscoll
Keyword(s):  
Growth Hormone ◽  
Body Composition ◽  
Transition Period ◽  
Neurodevelopmental Disorder ◽  
Hormone Treatment ◽  
Psychomotor Development ◽  
Prader Willi Syndrome ◽  
Gh Treatment ◽  
Beneficial Effects ◽  
Positive Effects

AbstractPrader-Willi syndrome (PWS) is a complex, multi-system, neurodevelopmental disorder characterised by neonatal muscular hypotonia, short stature, high risk of obesity, hypogonadism, intellectual disabilities, distinct behavioural/psychiatric problems and abnormal body composition with increased body fat and a deficit of lean body mass. Growth hormone (GH) deficiency and other hormone deficiencies are common due to hypothalamic dysfunction. In children with PWS GH treatment has been widely demonstrated to improve body composition, normalise height and improve psychomotor development. In adults with PWS, GH’s main effects are to maintain normal body structure and metabolism. The positive effects of GH treatment on body composition, physical fitness and beneficial effects on cardiovascular risk markers, behaviour and quality of life in adults with PWS are also well established from several studies. GH treatment is approved for treatment of children with PWS in many countries, but until recently not as a treatment in young adults in the transition period or for adults in general. In this commentary we want to draw attention to the uneven global use of GH treatment, specifically in adults with PWS, and advocate for GH treatment to be approved internationally, not just for children, but also for adults with PWS and based only on the diagnosis of genetically confirmed PWS.

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