{"title":"糖尿病和肥胖易感基因:来自巴基斯坦卡拉奇的甲基化模式的横断面分析。","authors":"Syeda Sadia Fatima, Asad Saulat Fatimi, Manzar Abbas, Unab I Khan","doi":"10.1093/postmj/qgaf016","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose of study: </strong>Environmental factors are pivotal in shaping disease outcomes for obesity, diabetes, and metabolic syndrome (MetS), especially in the Pakistani population. This study aimed to determine whether promoter methylation levels of 12 diabetes and obesity susceptibility genes are associated with MetS phenotypes and risk of T2DM in Pakistani individuals.</p><p><strong>Study design: </strong>A cross-sectional study was undertaken whereby methylation-specific PCR assays were conducted on 203 adult subjects recruited from the community in Karachi, Pakistan. Participants were stratified into four groups based on their metabolic health and BMI (MOU n = 39, MHO n = 43, MUHNW n = 51, MHNW n = 70). Biochemical and biophysical data were statistically analyzed to determine the association of methylation levels with MetS phenotypes.</p><p><strong>Results: </strong>Low chemerin promoter methylation was observed in metabolically unhealthy participants, irrespective of BMI, while higher methylation levels were observed for POMC and PCSK1. Unsupervised machine learning showed that the methylation status of Chemerin, IGF2, POMC, PCSK1 (P < .001), and FNDC (P < .05) was independently linked with the risk of developing MetS. Hierarchical clustering analysis revealed distinct genetic clusters that partially aligned with the original MetS and BMI categories, indicating the presence of unique genetic profiles and the potential misdiagnosis of high-risk individuals.</p><p><strong>Conclusion: </strong>Chemerin, IGF2, POMC, PCSK1, and FNDC's methylation status shows independently linked trends with the risk of developing MetS and obesity. Distinct genetic clusters for MUHNW and MHO exhibit similar phenotypic profiles, implying misdiagnosis risks and comparable risks of developing cardiometabolic disorders in the future. Large-scale methylation studies are needed to confirm the association. Key message What is already known on this topic: Genetic susceptibility contributes significantly to complex disorders like obesity, diabetes, and MetS. Prior research has highlighted the role of genetic polymorphisms but hasn't extensively explored the influence of promoter methylation in Pakistani populations. Understanding genetic and epigenetic factors in disease etiology is crucial for tailored interventions, particularly in populations with diverse genetic backgrounds and environmental exposures. What this study adds: Distinct trends of methylation patterns were observed in genes like Chemerin, IGF2, POMC, PCSK1, and FNDC, independently linked with MetS and obesity risk. Potential misdiagnosis risks and comparable risks of developing cardiometabolic disorders in individuals with metabolically unhealthy normal weight individuals and metabolically healthy phenotypes were observed. How this study might affect research, practice, or policy: Incorporating epigenetic biomarkers into risk assessment algorithms could enhance disease prediction accuracy and facilitate early intervention strategies. Recognizing misdiagnosis risks associated with MUHNW and MHO phenotypes could inform clinical practice and public health policies for improved disease screening and management.</p>","PeriodicalId":20374,"journal":{"name":"Postgraduate Medical Journal","volume":" ","pages":""},"PeriodicalIF":3.6000,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Diabetes and obesity susceptibility genes: a cross-sectional analysis of methylation patterns from Karachi, Pakistan.\",\"authors\":\"Syeda Sadia Fatima, Asad Saulat Fatimi, Manzar Abbas, Unab I Khan\",\"doi\":\"10.1093/postmj/qgaf016\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose of study: </strong>Environmental factors are pivotal in shaping disease outcomes for obesity, diabetes, and metabolic syndrome (MetS), especially in the Pakistani population. This study aimed to determine whether promoter methylation levels of 12 diabetes and obesity susceptibility genes are associated with MetS phenotypes and risk of T2DM in Pakistani individuals.</p><p><strong>Study design: </strong>A cross-sectional study was undertaken whereby methylation-specific PCR assays were conducted on 203 adult subjects recruited from the community in Karachi, Pakistan. Participants were stratified into four groups based on their metabolic health and BMI (MOU n = 39, MHO n = 43, MUHNW n = 51, MHNW n = 70). Biochemical and biophysical data were statistically analyzed to determine the association of methylation levels with MetS phenotypes.</p><p><strong>Results: </strong>Low chemerin promoter methylation was observed in metabolically unhealthy participants, irrespective of BMI, while higher methylation levels were observed for POMC and PCSK1. Unsupervised machine learning showed that the methylation status of Chemerin, IGF2, POMC, PCSK1 (P < .001), and FNDC (P < .05) was independently linked with the risk of developing MetS. Hierarchical clustering analysis revealed distinct genetic clusters that partially aligned with the original MetS and BMI categories, indicating the presence of unique genetic profiles and the potential misdiagnosis of high-risk individuals.</p><p><strong>Conclusion: </strong>Chemerin, IGF2, POMC, PCSK1, and FNDC's methylation status shows independently linked trends with the risk of developing MetS and obesity. Distinct genetic clusters for MUHNW and MHO exhibit similar phenotypic profiles, implying misdiagnosis risks and comparable risks of developing cardiometabolic disorders in the future. Large-scale methylation studies are needed to confirm the association. Key message What is already known on this topic: Genetic susceptibility contributes significantly to complex disorders like obesity, diabetes, and MetS. Prior research has highlighted the role of genetic polymorphisms but hasn't extensively explored the influence of promoter methylation in Pakistani populations. Understanding genetic and epigenetic factors in disease etiology is crucial for tailored interventions, particularly in populations with diverse genetic backgrounds and environmental exposures. What this study adds: Distinct trends of methylation patterns were observed in genes like Chemerin, IGF2, POMC, PCSK1, and FNDC, independently linked with MetS and obesity risk. Potential misdiagnosis risks and comparable risks of developing cardiometabolic disorders in individuals with metabolically unhealthy normal weight individuals and metabolically healthy phenotypes were observed. How this study might affect research, practice, or policy: Incorporating epigenetic biomarkers into risk assessment algorithms could enhance disease prediction accuracy and facilitate early intervention strategies. Recognizing misdiagnosis risks associated with MUHNW and MHO phenotypes could inform clinical practice and public health policies for improved disease screening and management.</p>\",\"PeriodicalId\":20374,\"journal\":{\"name\":\"Postgraduate Medical Journal\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2025-02-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Postgraduate Medical Journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/postmj/qgaf016\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, GENERAL & INTERNAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Postgraduate Medical Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/postmj/qgaf016","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
引用次数: 0
摘要
研究目的:环境因素是影响肥胖、糖尿病和代谢综合征(MetS)疾病结局的关键因素,尤其是在巴基斯坦人群中。本研究旨在确定12种糖尿病和肥胖易感基因的启动子甲基化水平是否与巴基斯坦个体的MetS表型和2型糖尿病风险相关。研究设计:进行了一项横断面研究,对从巴基斯坦卡拉奇社区招募的203名成人受试者进行了甲基化特异性PCR检测。根据代谢健康状况和BMI指数将参与者分为四组(MOU n = 39, MHO n = 43, MUHNW n = 51, MHNW n = 70)。对生化和生物物理数据进行统计分析,以确定甲基化水平与MetS表型的关系。结果:在代谢不健康的参与者中,无论BMI如何,都观察到低的趋化素启动子甲基化,而POMC和PCSK1的甲基化水平较高。无监督机器学习显示Chemerin、IGF2、POMC、PCSK1的甲基化状态(P结论:Chemerin、IGF2、POMC、PCSK1和FNDC的甲基化状态与发生MetS和肥胖的风险有独立的相关趋势。MUHNW和MHO的不同遗传集群表现出相似的表型特征,这意味着误诊风险和未来发生心脏代谢疾病的风险相当。需要大规模的甲基化研究来证实这种关联。关于该主题的已知信息:遗传易感性对肥胖、糖尿病和MetS等复杂疾病有重要影响。先前的研究强调了遗传多态性的作用,但尚未广泛探索启动子甲基化在巴基斯坦人群中的影响。了解疾病病因学中的遗传和表观遗传因素对于有针对性的干预措施至关重要,特别是在具有不同遗传背景和环境暴露的人群中。这项研究补充的内容:在Chemerin、IGF2、POMC、PCSK1和FNDC等基因中观察到明显的甲基化模式趋势,这些基因与MetS和肥胖风险独立相关。观察了代谢不健康的正常体重个体和代谢健康表型个体发生心脏代谢紊乱的潜在误诊风险和可比风险。本研究对研究、实践或政策的影响:将表观遗传生物标志物纳入风险评估算法可以提高疾病预测的准确性,并促进早期干预策略。认识到与MUHNW和MHO表型相关的误诊风险可以为临床实践和公共卫生政策提供信息,以改进疾病筛查和管理。
Diabetes and obesity susceptibility genes: a cross-sectional analysis of methylation patterns from Karachi, Pakistan.
Purpose of study: Environmental factors are pivotal in shaping disease outcomes for obesity, diabetes, and metabolic syndrome (MetS), especially in the Pakistani population. This study aimed to determine whether promoter methylation levels of 12 diabetes and obesity susceptibility genes are associated with MetS phenotypes and risk of T2DM in Pakistani individuals.
Study design: A cross-sectional study was undertaken whereby methylation-specific PCR assays were conducted on 203 adult subjects recruited from the community in Karachi, Pakistan. Participants were stratified into four groups based on their metabolic health and BMI (MOU n = 39, MHO n = 43, MUHNW n = 51, MHNW n = 70). Biochemical and biophysical data were statistically analyzed to determine the association of methylation levels with MetS phenotypes.
Results: Low chemerin promoter methylation was observed in metabolically unhealthy participants, irrespective of BMI, while higher methylation levels were observed for POMC and PCSK1. Unsupervised machine learning showed that the methylation status of Chemerin, IGF2, POMC, PCSK1 (P < .001), and FNDC (P < .05) was independently linked with the risk of developing MetS. Hierarchical clustering analysis revealed distinct genetic clusters that partially aligned with the original MetS and BMI categories, indicating the presence of unique genetic profiles and the potential misdiagnosis of high-risk individuals.
Conclusion: Chemerin, IGF2, POMC, PCSK1, and FNDC's methylation status shows independently linked trends with the risk of developing MetS and obesity. Distinct genetic clusters for MUHNW and MHO exhibit similar phenotypic profiles, implying misdiagnosis risks and comparable risks of developing cardiometabolic disorders in the future. Large-scale methylation studies are needed to confirm the association. Key message What is already known on this topic: Genetic susceptibility contributes significantly to complex disorders like obesity, diabetes, and MetS. Prior research has highlighted the role of genetic polymorphisms but hasn't extensively explored the influence of promoter methylation in Pakistani populations. Understanding genetic and epigenetic factors in disease etiology is crucial for tailored interventions, particularly in populations with diverse genetic backgrounds and environmental exposures. What this study adds: Distinct trends of methylation patterns were observed in genes like Chemerin, IGF2, POMC, PCSK1, and FNDC, independently linked with MetS and obesity risk. Potential misdiagnosis risks and comparable risks of developing cardiometabolic disorders in individuals with metabolically unhealthy normal weight individuals and metabolically healthy phenotypes were observed. How this study might affect research, practice, or policy: Incorporating epigenetic biomarkers into risk assessment algorithms could enhance disease prediction accuracy and facilitate early intervention strategies. Recognizing misdiagnosis risks associated with MUHNW and MHO phenotypes could inform clinical practice and public health policies for improved disease screening and management.
期刊介绍:
Postgraduate Medical Journal is a peer reviewed journal published on behalf of the Fellowship of Postgraduate Medicine. The journal aims to support junior doctors and their teachers and contribute to the continuing professional development of all doctors by publishing papers on a wide range of topics relevant to the practicing clinician and teacher. Papers published in PMJ include those that focus on core competencies; that describe current practice and new developments in all branches of medicine; that describe relevance and impact of translational research on clinical practice; that provide background relevant to examinations; and papers on medical education and medical education research. PMJ supports CPD by providing the opportunity for doctors to publish many types of articles including original clinical research; reviews; quality improvement reports; editorials, and correspondence on clinical matters.