Lifestyle Genomics最新文献

{"title":"Redefining Malignant Hyperthermia: Multi-omics Insights into a Complex Anesthetic Disorder.","authors":"Cassandra Thachuk, Darragh Barry, Jackie Trink","doi":"10.1159/000548601","DOIUrl":"https://doi.org/10.1159/000548601","url":null,"abstract":"<p><p>Malignant hyperthermia (MH) is a rare but serious pharmacogenetic disorder triggered by specific anesthetic agents, leading to a rapid and often fatal hypermetabolic response. While its genetic roots-primarily involving RYR1 and CACNA1S mutations-are well documented, many susceptible individuals remain undiagnosed until they are exposed to the triggering anesthetic. Despite dantrolene being an instrumental drug in combatting MH mortality, global access remains inconsistent, and morbidity rates remains high. Current diagnostic tools are invasive and limited to specialized centers, and routine screening is rarely feasible. This review explores how recent advances in multi-omics-genomics, proteomics, metabolomics, transcriptomics, and radiomics-are reshaping our understanding of MH pathophysiology. From chronic calcium dysregulation and mitochondrial dysfunction to shifts in energy metabolism and subtle muscle changes, a complex picture is emerging. Integrative analyses reveal promising biomarkers for early detection, while CRISPR-based gene editing and machine learning offer potential pathways for future targeted interventions. Non-invasive imaging, blood-based metabolic profiling, and genomic risk prediction may soon offer safer, more effective screening tools for anesthesia planning. Ultimately, a shift from reactive crisis management to proactive risk identification could redefine how we approach MH-potentially improving patient outcomes and saving lives.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":" ","pages":"1-12"},"PeriodicalIF":1.4,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Klotho, Kidneys and Micronutrient Signaling, a Promising Paradigm for Healthy Aging.","authors":"Sara Mahdavi","doi":"10.1159/000548666","DOIUrl":"https://doi.org/10.1159/000548666","url":null,"abstract":"<p><p>Klotho, a transmembrane protein with pleiotropic anti-aging properties, is increasingly recognized as a central regulator of longevity and metabolic resilience. Primarily expressed in the kidneys and brain, Klotho governs phosphate and calcium homeostasis, modulates redox signaling, and influences key metabolic pathways, including PI3K/AKT and IGF-1. Declining Klotho expression is associated with both biological and chronological aging and has been mechanistically implicated in the pathogenesis of chronic kidney disease (CKD), cardiovascular disease (CVD), neurodegeneration, and metabolic dysfunction. Klotho expression is modifiable through diet, in preclinical and observational offering a promising avenue for delaying cellular aging and preserving physiological function. Micronutrients such as magnesium, vitamin D, folate, and vitamin B12, as well as phytochemicals including sulforaphane and curcumin, have been shown to modulate Klotho expression through redox-sensitive and transcriptional mechanisms. Macronutrient balance-particularly carbohydrate quality and saturated fat intake-also plays a critical role in maintaining Klotho activity via insulin sensitivity, mitochondrial integrity, and inflammatory signaling. Inflammatory dietary profiles, quantified through tools such as the Dietary Inflammatory Index (DII), have been inversely associated with serum α-Klotho concentrations and biological age acceleration. This review critically synthesizes current knowledge on nutrient-specific and dietary pattern-level influences on Klotho, with emphasis on antioxidant, anti-inflammatory, and epigenetically active compounds. In parallel, the Klotho-FGF23 axis is examined regarding dietary calcium and phosphate regulation, highlighting the distinct effects of whole food-derived versus supplemental calcium on mineral metabolism and vascular health. Klotho emerges as a potential modifiable determinant and current limitations as a potential biomarker within precision nutrition strategies aimed at extending health-span and attenuating age-related disease risk. Key concepts discussed include dietary factors in klotho modulation and chronic disease Prevention, as well as opportunities and limitations of soluble klotho as a multifaceted biomarker of human health and longevity.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":" ","pages":"1-17"},"PeriodicalIF":1.4,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning-based prediction of gout using polygenic risk scores and clinical variables: A Korean cohort study.","authors":"Do-Hyeon Kwak, Hyunjung Kim, Hee-Won Park, Sun Shim Choi, Ki Won Moon","doi":"10.1159/000548169","DOIUrl":"https://doi.org/10.1159/000548169","url":null,"abstract":"<p><p>The prevalence of gout, a chronic metabolic disease, has recently increased. Polygenic risk scores (PRS) represent a useful tool for predicting patient outcomes of this condition. However, the clinical utility of PRS in disease prediction remains controversial. Using data from the Korean Genome and Epidemiology Study, machine learning (ML) models were developed to predict gout based on PRS and clinical variables such as uric acid, lifestyle habits, and metabolic syndrome (MetS) profiles. Five supervised learning algorithms were applied: logistic regression (a traditional statistical model often used in machine learning contexts), random forest (RF), decision tree (DT), extreme gradient boosting, and light gradient boosting. Among the models, the RF model incorporating PRS, age, sex, MetS, and uric acid levels achieved the highest area under the curve (0.7204, 95% CI = 0.7124-0.7284). Feature importance analysis highlighted uric acid levels as the most important predictor of gout, followed by PRS and age. Although PRS enhanced the predictive power of the ML models, its effect was modest, suggesting that traditional risk factors remain important for gout prediction. This study demonstrated that integrating genetic data with clinical variables improves gout prediction. Further research is necessary to optimize the utility of PRS in diverse populations.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":" ","pages":"1-18"},"PeriodicalIF":1.4,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145149789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current Evidence and Outlook Regarding the Combined Effects of Fructose Consumption, Obesity Status, and Genetic Variation on C-reactive Protein.","authors":"Tamara K Reed","doi":"10.1159/000547980","DOIUrl":"https://doi.org/10.1159/000547980","url":null,"abstract":"","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":" ","pages":"1-9"},"PeriodicalIF":1.4,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linking dietary creatine to DNA methylation-based predictors of mortality in individuals aged 50 and above.","authors":"Sergej M Ostojic, Ivana Kavecan","doi":"10.1159/000547260","DOIUrl":"10.1159/000547260","url":null,"abstract":"<p><strong>Background: </strong>Creatine is a conditionally essential nutrient integral to cellular energy homeostasis, with emerging evidence suggesting its potential role in modulating biological aging. However, associations between dietary creatine intake and epigenetic biomarkers of mortality remain unexplored.</p><p><strong>Objective: </strong>This study investigates the relationship between dietary creatine intake and DNA methylation-derived mortality indices in U.S. adults aged 50 years and older.</p><p><strong>Methods: </strong>Data from the NHANES 1999-2002 cycles were analyzed, including dietary creatine intake estimated from 24-hour recall interviews and DNA methylation profiles measured using the Illumina EPIC array. Epigenetic mortality predictors GrimAgeMort and GrimAge2Mort were examined in relation to creatine intake.</p><p><strong>Results: </strong>Among 4,983 participants (mean age 67.6 ± 10.7 years), a significant inverse correlation was observed between dietary creatine and both GrimAgeMort (r = -0.041, P = 0.045) and GrimAge2Mort (r = -0.047, P = 0.019), indicating that higher creatine consumption was associated with lower epigenetic mortality risk scores. These associations persisted as statistically significant after adjustment for demographic variables and pertinent dietary factors.</p><p><strong>Conclusions: </strong>Higher dietary creatine intake is linked to reduced biological age acceleration and mortality risk as estimated by epigenetic biomarkers. These findings highlight creatine's potential as a modifiable dietary factor promoting healthy aging and longevity. Further research is warranted to elucidate underlying mechanisms.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":" ","pages":"1-8"},"PeriodicalIF":1.4,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precision nutrition and nutriomics in the machine learning era.","authors":"Omar Ramos-Lopez, Begoña de Cuevillas, Maria P Portillo, J Alfredo Martinez","doi":"10.1159/000546650","DOIUrl":"https://doi.org/10.1159/000546650","url":null,"abstract":"","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":" ","pages":"1-10"},"PeriodicalIF":2.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nicotine Metabolism-Related Genetic Polymorphisms Associated with Smoking Cessation in Korean Men: A Candidate Gene Association Study in a Korean Cohort.","authors":"Jae-Min Park, Ja-Eun Choi, Ji-Won Lee, Kyung-Won Hong","doi":"10.1159/000543543","DOIUrl":"10.1159/000543543","url":null,"abstract":"<p><strong>Introduction: </strong>Smoking cessation is influenced by genetic and environmental factors, particularly genetic polymorphisms influencing nicotine metabolism. This study investigated the association between specific nicotine metabolism-related genetic variants and smoking cessation among Korean men.</p><p><strong>Methods: </strong>A candidate gene association study was performed targeting single nucleotide polymorphisms (SNPs) within nicotine metabolism-related genes. Participants were categorized as never, former, or current smokers. A Genetic Risk Score (GRS) was computed using significant SNPs to evaluate cumulative genetic influence.</p><p><strong>Results: </strong>Six SNPs showed significant association with smoking cessation in a Korean cohort. A higher GRS was associated with increased odds of current smoking compared to former smoking (OR = 1.18, 95% CI: 1.12-1.25, p < 0.001).</p><p><strong>Conclusion: </strong>This study indicates a substantial genetic component in smoking cessation, highlighting the importance of population-specific approaches, and may aid personalized smoking cessation strategies based on genetic predisposition among Koreans.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":" ","pages":"20-26"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Experimental Environment Is a Determinant of Gene Methylation and One-Carbon Metabolism in Obese Adult Mice.","authors":"Zeyu Yang, Ruslan Kubant, Eva Kranenburg, Clara E Cho, G Harvey Anderson","doi":"10.1159/000546727","DOIUrl":"10.1159/000546727","url":null,"abstract":"<p><strong>Background: </strong>Diet-induced obesity (DIO) leads to insulin resistance (IR) and alters gene expression through epigenetic mechanisms, including DNA methylation. Here, we aimed to investigate whether experimental environment is an important variable in determining DNA methylation and one-carbon metabolism in DIO mice fed a multi-vitamin-mineral mixture (MVM).</p><p><strong>Methods: </strong>Three experiments with identical design were conducted in three independent animal facilities (i.e., experimental environments or locations). In each location, 12-week-old male C57BL/6J mice were randomly assigned to two dietary groups: high-fat (HF) and HF-MVM for an average of 10 weeks. Global and gene-specific methylation of adipose function related genes in epididymal white adipose tissue (eWAT), and insulin signaling genes in the liver were analyzed using bisulfite pyrosequencing. Hepatic 1-C metabolites were measured and the ratio of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) was used as an indicator of methylation potential.</p><p><strong>Results: </strong>Experimental location affected global methylation patterns in the eWAT, but not in the liver. At the gene-specific level, experimental location, MVM, and their interaction altered the methylation of genes related to adipose function (Srebf1, Acaca, Fasn, Pparg, and Rbp4) in the eWAT and insulin signaling (Pi3kr1 and Akt1) in the liver (p < 0.05). The SAM/SAH ratio was correlated with gene-specific methylation at some CpG sites of Srebf1, Pi3kr1, Acaca, Fasn, Pparg, Rbp4, and Akt1) genes (p < 0.05).</p><p><strong>Conclusion: </strong>The experimental environment is a significant determinant of the effects of micronutrient supplement on 1-C metabolism and the methylation of genes associated with IR in tissues of DIO adult male mice.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":" ","pages":"116-130"},"PeriodicalIF":1.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144506073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Differentially Methylated Genes among Preterm Birth and Full-Term Birth.","authors":"Aleem Razzaq, Razan ElKahlout, Gheyath K Nasrallah, Faisal E Ibrahim, Muthanna Samara, Hatem Zayed, Palli Valapila Abdulrouf, Rana Al-Jurf, Ahmed Najjar, Thomas Farrell, M Walid Qoronfleh, Hilal Al Rifai, Nader Al-Dewik","doi":"10.1159/000543372","DOIUrl":"10.1159/000543372","url":null,"abstract":"<p><strong>Introduction: </strong>Preterm birth (PTB) is a major contributor to neonatal morbidity and mortality. DNA methylation plays a critical role in fetal development and may serve as an epigenetic biomarker for PTB. However, few epigenetic studies have investigated PTB-specific DNA methylation changes. This study aimed to identify epigenetic differences between PTB and term birth (TB) infants.</p><p><strong>Methods: </strong>A total of 218 cord blood samples from three independent PTB studies were analyzed to identify epigenetic differences between PTB and TB infants. Differential methylation analysis was conducted while adjusting for key covariates, including gestational age, sex, and disease status. Differentially methylated regions (DMRs) (genes and promoters) and differentially methylated sites (DMSs) (CpG sites) were assessed for significant methylation differences between the two groups.</p><p><strong>Results: </strong>In PTB infants, several genes, including RNASE3, HGF, CLEC5A, LIPN, NXF1, and CCDC12 showed significant hypermethylation (p < 0.05), while the MUC20 and IFNL4 genes showed significant hypomethylation (p < 0.05). The eForge analysis revealed that hypermethylated (p < 0.05) CpG sites were significantly enriched in different fetal tissues such as the small and large intestines, adrenal gland, fetal heart, lungs, and kidney, whereas hypomethylated CpGs showed no significant enrichment. Gene ontology analysis indicated that differentially methylated genes were primarily involved in immune response regulation. Notably, S100A9 and S100A8 genes, which play crucial roles in neonatal immune function and sepsis risk, were hypermethylated (p < 0.05) in PTB infants.</p><p><strong>Conclusion: </strong>This study identified PTB-associated DNA methylation changes in immune-related genes, suggesting their potential epigenetic biomarkers for PTB. These findings enhance our understanding of PTB pathogenesis and may contribute to the development of novel diagnostic and therapeutic strategies.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":" ","pages":"76-89"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12097759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CC Genotype at TCF7L2 Diabetes Risk Locus rs7903146 Directs a Coordinated Fatty Acid Response to a Mediterranean Diet Intervention: A Randomized Controlled Trial.","authors":"Laurence D Parnell, Chao-Qiang Lai, Christina Holzapfel, Jacob J Christensen, José M Ordovás","doi":"10.1159/000542468","DOIUrl":"10.1159/000542468","url":null,"abstract":"<p><strong>Introduction: </strong>Previous studies identified genetic links between the TCF7L2 C/T variant rs7903146, type 2 diabetes (T2D), and obesity. We wished to deepen our understanding of how specific diets interact with this variant to affect blood metabolites, an aspect not previously investigated. Hence, we conducted a controlled study where individuals with different genotypes followed a Mediterranean (Med) or low-fat (LF) diet for 1 week.</p><p><strong>Methods: </strong>Participants were recruited from the Boston, MA (USA) area. Anthropometric and clinical measures were taken. Genotypes at rs7903146 were ascertained, with homozygous carriers of the more common and protective CC or risk TT genotype invited to participate. Participants followed both diets (LF or Med) for 1 week with ∼10 days' washout between diets. Blood samples taken at the beginning and end of each diet period underwent metabolomics analysis using nuclear magnetic resonance spectroscopy. We evaluated how the diet affected different metabolites based on genetic profile.</p><p><strong>Results: </strong>The cohort of 35 persons was 43% female, aged 18-70 y, with BMI between 26.4 and 33.9 kg/m2. Focusing on fatty acids (FAs) and other lipid metabolic factors (n = 23), we observed a greater number and stronger correlations among these factors in the CC genotype-Med diet group than in the other three genotype-diet combinations. An aggregate of 11 factors, each negatively correlating with delta-saturated fatty acids (SFA), showed a significant genotype-Med diet interaction on delta-SFA in CC individuals on the Med diet (p = 0.0046). A similar genotype-Med diet interaction was observed for delta-monounsaturated fatty acids (p = 0.0078). These interactions were not statistically significant at the end of the LF intervention.</p><p><strong>Conclusion: </strong>Our findings suggest that the Med diet has a stronger influence on regulating lipid factors in individuals with the CC genotype at the TCF7L2 variant rs7903146. This diet-genotype interaction may have significant implications for understanding the inter-individual variation of metabolic response on specific dietary regimens.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":" ","pages":"36-51"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}