{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T14:43:47Z","timestamp":1782917027312,"version":"3.54.5"},"reference-count":37,"publisher":"Scientific Scholar","content-domain":{"domain":["ijmr.org.in"],"crossmark-restriction":true},"short-container-title":["Indian J Med Res"],"abstract":"<jats:sec>\n                    <jats:title>Background and objectives<\/jats:title>\n                    <jats:p>Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine-metabolic disorder with unclear etiology, influenced by genetic, environmental, and epigenetic factors. This study investigated the role of gene-specific DNA methylation and transcriptional regulation in North Indian women with PCOS stratified by body mass index (BMI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Thirty women with PCOS (19 obese, 11 non-obese) and 10 healthy controls (age-matched to both PCOS groups; BMI-matched to non-obese PCOS) were recruited. BMI stratification was intentional to assess obesity-specific epigenetic modifications. Clinical, hormonal, and metabolic parameters were assessed. Promoter-methylation and mRNA expression of 17 candidate genes involved in epigenetic regulation, steroidogenesis, insulin signalling, and cell proliferation were analysed using methylation-specific PCR and qRT-PCR. Correlation matrices were constructed to evaluate associations between methylation and clinical traits. Receiver operating characteristic (ROC) based modelling was used to assess the predictive utility of methylation markers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PCOS-obese participants exhibited significantly elevated testosterone, Luteinising Hormone (LH), and cholesterol levels compared to controls. Vitamin D\u2083 deficiency was observed in both PCOS subgroups. Epigenetic analysis revealed hypermethylation and downregulation of\n                      <jats:italic>TET1<\/jats:italic>\n                      and\n                      <jats:italic>INSIG1<\/jats:italic>\n                      , and hypomethylation-linked overexpression of\n                      <jats:italic>SF1, CYP11A1,<\/jats:italic>\n                      and cell cycle regulators. Correlation analyses revealed associative methylation expression signatures linked with key hormonal parameters (\n                      <jats:italic>e.g<\/jats:italic>\n                      ., testosterone, LH\/FSH ratio) and, to a lesser extent, metabolic traits (associative findings but not mechanistic conclusions).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation and conclusions<\/jats:title>\n                    <jats:p>This integrative study highlights distinct methylation-expression signatures as hypothesis-generating markers that show statistical association with certain clinical traits, particularly in the obese-PCOS subgroup, but require validation in larger cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.25259\/ijmr_2980_2025","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T12:59:43Z","timestamp":1782910783000},"page":"103-113","update-policy":"https:\/\/doi.org\/10.25259\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["BMI-dependent methylation and clinical signatures in North Indian women with PCOS"],"prefix":"10.25259","volume":"164","author":[{"given":"Kajal","family":"Rawat","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arushi","family":"Sandhu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lekha","family":"Saha","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rama","family":"Walia","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Postgraduate Institute of Medical Education and Research, Chandigarh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradip","family":"Kumar Saha","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Postgraduate Institute of Medical Education and Research, Chandigarh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alka","family":"Bhatia","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10894","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"10.25259\/IJMR_2980_2025\/ref-1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.fertnstert.2003.10.004","article-title":"Rotterdam ESHRE\/ASRM-Sponsored PCOS Consensus Workshop Group.Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome","volume":"81","year":"2004","journal-title":"Fertil Steril."},{"key":"10.25259\/IJMR_2980_2025\/ref-2","doi-asserted-by":"publisher","first-page":"261","DOI":"10.4103\/jhrs.JHRS_95_18","article-title":"The prevalence of polycystic ovary syndrome: A brief systematic review","volume":"13","author":"Deswal","year":"2020","journal-title":"J Hum Reprod Sci."},{"key":"10.25259\/IJMR_2980_2025\/ref-3","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1210\/er.2011-1034","article-title":"Insulin resistance and the polycystic ovary syndrome revisited: An update on mechanisms and implications","volume":"33","author":"Diamanti-Kandarakis","year":"2012","journal-title":"Endocr Rev."},{"key":"10.25259\/IJMR_2980_2025\/ref-4","doi-asserted-by":"publisher","first-page":"2038","DOI":"10.1210\/jc.2009-2724","article-title":"Assessment of cardiovascular risk and prevention of cardiovascular disease in women with the polycystic ovary syndrome: A consensus statement by the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society","volume":"95","author":"Wild","year":"2010","journal-title":"J Clin Endocrinol Metab."},{"key":"10.25259\/IJMR_2980_2025\/ref-5","doi-asserted-by":"publisher","first-page":"gaac024","DOI":"10.1093\/molehr\/gaac024","article-title":"Role of genomic DNA methylation in PCOS pathogenesis: A systematic review and meta-analysis involving case-controlled clinical studies","volume":"28","author":"Rawat","year":"2022","journal-title":"Mol Hum Reprod."},{"key":"10.25259\/IJMR_2980_2025\/ref-6","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.reprotox.2022.04.010","article-title":"DNA methylation in polycystic ovary syndrome: Emerging evidence and challenges","volume":"111","author":"Liu","year":"2022","journal-title":"Reprod Toxicol."},{"key":"10.25259\/IJMR_2980_2025\/ref-7","doi-asserted-by":"publisher","first-page":"R27","DOI":"10.1530\/REP-18-0449","article-title":"DNA methylation in the pathogenesis of polycystic ovary syndrome","volume":"158","author":"V\u00e1zquez-Mart\u00ednez","year":"2019","journal-title":"Reproduction."},{"key":"10.25259\/IJMR_2980_2025\/ref-8","doi-asserted-by":"publisher","first-page":"730","DOI":"10.3390\/biomedicines13030730","article-title":"Epigenetic alterations in ovarian function and theirimpact on assisted reproductive technologies: A systematic review","volume":"13","author":"Voros","year":"2025","journal-title":"Biomedicines."},{"key":"10.25259\/IJMR_2980_2025\/ref-9","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1007\/s43032-022-01013-x","article-title":"Updates on molecular targets and epigenetic-based therapies for PCOS","volume":"30","author":"Smirnov","year":"2023","journal-title":"Reprod Sci."},{"key":"10.25259\/IJMR_2980_2025\/ref-10","doi-asserted-by":"crossref","first-page":"14663","DOI":"10.3390\/ijms232314663","article-title":"Modulation of the Inflammatory Response in polycystic ovary syndrome (PCOS)\u2014Searching for epigenetic factors","volume":"23","author":"Szukiewicz","year":"2022","journal-title":"IJMS."},{"key":"10.25259\/IJMR_2980_2025\/ref-11","doi-asserted-by":"publisher","first-page":"22883","DOI":"10.1038\/srep22883","article-title":"Epigenetic and Transcriptional Alterations in Human Adipose Tissue of Polycystic Ovary Syndrome","volume":"6","author":"Kokosar","year":"2016","journal-title":"Sci Rep"},{"key":"10.25259\/IJMR_2980_2025\/ref-12","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1093\/humupd\/dmu060","article-title":"Obesity and the reproductive system disorders: Epigenetics as a potential bridge","volume":"21","author":"Crujeiras","year":"2015","journal-title":"Hum Reprod Update."},{"key":"10.25259\/IJMR_2980_2025\/ref-13","doi-asserted-by":"publisher","first-page":"800","DOI":"10.2174\/0929867327666200824112056","article-title":"Obesity and insulin resistance: Associations with chronic inflammation, genetic and epigenetic factors","volume":"28","author":"Gasmi","year":"2021","journal-title":"Curr Med Chem."},{"key":"10.25259\/IJMR_2980_2025\/ref-14","doi-asserted-by":"crossref","first-page":"7","DOI":"10.4103\/ijt.ijt_93_16","article-title":"Modified Ferriman\u2013Gallwey score in hirsutism and its association with metabolic syndrome","volume":"9","author":"Jayapalan","year":"2017","journal-title":"Int J Trichol."},{"key":"10.25259\/IJMR_2980_2025\/ref-15","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1016\/j.cmet.2021.01.004","article-title":"Polycystic ovary syndrome is transmitted via a transgenerational epigenetic process","volume":"33","author":"Mimouni","year":"2021","journal-title":"Cell Metab."},{"key":"10.25259\/IJMR_2980_2025\/ref-16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13148-018-0606-9","article-title":"DNA methylome profiling of granulosa cells reveals altered methylation in genes regulating vital ovarian functions in polycystic ovary syndrome","volume":"11","author":"Sagvekar","year":"2019","journal-title":"Clin Epigenetics."},{"key":"10.25259\/IJMR_2980_2025\/ref-17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13148-017-0434-3","article-title":"Aberrant expression and DNA methylation of lipid metabolism genes in PCOS: A new insight into its pathogenesis","volume":"10","author":"Pan","year":"2018","journal-title":"Clin Epigenetics."},{"key":"10.25259\/IJMR_2980_2025\/ref-18","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1007\/s00109-012-0881-4","article-title":"A molecular mechanism underlying ovarian dysfunction of polycystic ovary syndrome: Hyperandrogenism induces epigenetic alterations in the granulosa cells","volume":"90","author":"Qu","year":"2012","journal-title":"J Mol Med (Berl)."},{"key":"10.25259\/IJMR_2980_2025\/ref-19","doi-asserted-by":"publisher","first-page":"1010428317692205","DOI":"10.1177\/1010428317692205","article-title":"UHRF1: The key regulator of epigenetics and molecular target for cancer therapeutics","volume":"39","author":"Sidhu","year":"2017","journal-title":"Tumour Biol."},{"key":"10.25259\/IJMR_2980_2025\/ref-20","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1016\/j.cca.2020.05.042","article-title":"Emerging role of Insig-1 in lipid metabolism and lipid disorders","volume":"508","author":"Ouyang","year":"2020","journal-title":"Clin Chim Acta."},{"key":"10.25259\/IJMR_2980_2025\/ref-21","doi-asserted-by":"publisher","first-page":"147423","DOI":"10.1016\/j.gene.2023.147423","article-title":"The role of lamin B2 in human diseases","volume":"870","author":"LiY","year":"2023","journal-title":"Gene."},{"key":"10.25259\/IJMR_2980_2025\/ref-22","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s13148-020-0815-x","article-title":"Epigenetic silencing of IGFBPL1 promotes esophageal cancer growth by activating PI3K-AKT signaling","volume":"12","author":"Liu","year":"2020","journal-title":"Clin Epigenetics."},{"key":"10.25259\/IJMR_2980_2025\/ref-23","doi-asserted-by":"publisher","first-page":"350915","DOI":"10.31557\/apjcp.2023.24.10.3509","article-title":"Association of promoter methylation patterns with expression of MAPK14 in tissue of papillary thyroid cancer patients","volume":"24","author":"Shahdust","year":"2023","journal-title":"Asian Pac J Cancer Prev."},{"key":"10.25259\/IJMR_2980_2025\/ref-24","doi-asserted-by":"publisher","first-page":"E32","DOI":"10.1093\/nar\/28.8.e32","article-title":"MethyLight: A high-throughput assay to measure DNA methylation","volume":"28","author":"Eads","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"10.25259\/IJMR_2980_2025\/ref-25","doi-asserted-by":"publisher","first-page":"pdb.prot094847","DOI":"10.1101\/pdb.prot094847","article-title":"Methylation-specific polymerase chain reaction (PCR) for gene-specific DNA methylation detection","volume":"2017","author":"Lizardi","year":"2017","journal-title":"Cold Spring HarbProtoc."},{"key":"10.25259\/IJMR_2980_2025\/ref-26","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1111\/j.1365-2265.2006.02587.x","article-title":"Obesity and polycystic ovary syndrome","volume":"65","author":"Barber","year":"2006","journal-title":"Clin Endocrinol (Oxf)."},{"key":"10.25259\/IJMR_2980_2025\/ref-27","doi-asserted-by":"publisher","first-page":"271","DOI":"10.2217\/whe.09.89","article-title":"Polycystic ovary syndrome and weight management","volume":"6","author":"Moran","year":"2010","journal-title":"Womens Health (Lond)."},{"key":"10.25259\/IJMR_2980_2025\/ref-28","doi-asserted-by":"publisher","first-page":"1629","DOI":"10.3390\/nu16111629","article-title":"Obesity, dietary patterns, and hormonal balance modulation: Gender-specific impacts","volume":"16","author":"Mazza","year":"2024","journal-title":"Nutrients."},{"key":"10.25259\/IJMR_2980_2025\/ref-29","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/s13679-023-00531-2","article-title":"Hypothalamic-ovarian axis and adiposity relationship in polycystic ovary syndrome: Physiopathology and therapeutic options for the management ofmetabolic and inflammatory aspects","volume":"13","author":"Lonardo","year":"2024","journal-title":"Curr Obes Rep."},{"key":"10.25259\/IJMR_2980_2025\/ref-30","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1016\/j.metabol.2011.03.002","article-title":"Vitamin D deficiency is common and associated with metabolic risk factors in patients with polycystic ovary syndrome","volume":"60","author":"Li","year":"2011","journal-title":"Metabolism."},{"key":"10.25259\/IJMR_2980_2025\/ref-31","doi-asserted-by":"publisher","first-page":"3506","DOI":"10.1097\/MS9.0000000000000879","article-title":"Vitamin D and polycystic ovary syndrome (PCOS): A review","volume":"85","author":"Mohan","year":"2023","journal-title":"Ann Med Surg (Lond)."},{"key":"10.25259\/IJMR_2980_2025\/ref-32","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/j.cca.2019.11.003","article-title":"Polycystic ovarian syndrome: Correlation between hyperandrogenism, insulin resistance and obesity","volume":"502","author":"Zeng","year":"2020","journal-title":"Clin Chim Acta."},{"key":"10.25259\/IJMR_2980_2025\/ref-33","doi-asserted-by":"publisher","first-page":"1273542","DOI":"10.3389\/fendo.2023.1273542","article-title":"Androgen excess: A hallmark of polycystic ovary syndrome","volume":"14","author":"Wang","year":"2023","journal-title":"Front Endocrinol (Lausanne)."},{"key":"10.25259\/IJMR_2980_2025\/ref-34","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1038\/nrendo.2010.217","article-title":"Polycystic ovary syndrome: Etiology, pathogenesis and diagnosis","volume":"7","author":"Goodarzi","year":"2011","journal-title":"Nat Rev Endocrinol."},{"key":"10.25259\/IJMR_2980_2025\/ref-35","doi-asserted-by":"publisher","first-page":"2145","DOI":"10.1016\/j.peptides.2010.07.020","article-title":"Insulin-induced gene: A new regulator in lipid metabolism","volume":"31","author":"Dong","year":"2010","journal-title":"Peptides."},{"key":"10.25259\/IJMR_2980_2025\/ref-36","doi-asserted-by":"publisher","first-page":"2182","DOI":"10.1007\/s00125-020-05212-6","article-title":"Multi-layered epigenetic regulation of IRS2 expression in the liver of obese individuals with type 2 diabetes","volume":"63","author":"Krause","year":"2020","journal-title":"Diabetologia."},{"key":"10.25259\/IJMR_2980_2025\/ref-37","doi-asserted-by":"publisher","first-page":"101927","DOI":"10.1016\/j.genrep.2024.101927","article-title":"Genome-wide DNA methylation analysis in blood identifies differentially methylated regions related to polycystic ovary syndrome","volume":"35","author":"Sharma","year":"2024","journal-title":"Gene Reports."}],"container-title":["Indian Journal of Medical Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ijmr.org.in\/bmi-dependent-methylation-and-clinical-signatures-in-north-indian-women-with-pcos\/","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/ijmr.org.in\/bmi-dependent-methylation-and-clinical-signatures-in-north-indian-women-with-pcos\/","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T13:46:01Z","timestamp":1782913561000},"score":1,"resource":{"primary":{"URL":"http:\/\/ijmr.org.in\/bmi-dependent-methylation-and-clinical-signatures-in-north-indian-women-with-pcos\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,1]]},"references-count":37,"alternative-id":["10.25259\/IJMR_2980_2025"],"URL":"https:\/\/doi.org\/10.25259\/ijmr_2980_2025","relation":{},"ISSN":["0971-5916"],"issn-type":[{"value":"0971-5916","type":"print"}],"subject":[],"published":{"date-parts":[[2026,7,1]]},"article-number":"103"}}