Lifestyle Genomics最新文献

{"title":"Body Mass Index and Inter-Individual Variation in Salivary Amylase Gene Copy Number Assessed Using an In-House Validated Method: A Pilot Study from the National Nutrition Survey of a High Rice-Consuming Nation.","authors":"Mark Pretzel Zumaraga, Marietta Rodriguez, Charmaine Duante, Michael Serafico","doi":"10.1159/000549221","DOIUrl":"10.1159/000549221","url":null,"abstract":"<p><strong>Introduction: </strong>The AMY1 gene, which encodes salivary amylase, exhibits copy number variation (CNV) that affects starch metabolism and may influence obesity risk. This study aimed to assess AMY1 CNV among selected participants of the 2018-2019 Expanded National Nutrition Survey (ENNS), using a validated digital PCR method.</p><p><strong>Method: </strong>The method validation was initially performed using certified reference material. Whole blood DNA was isolated from selected nutrition survey respondents who had available daily rice intake data. The daily rice intake of participants was divided into tertiles. Chi-square tests were used to compare AMY1 CNV, age, BMI, smoking and alcohol status, and other variables across daily rice intake tertiles.</p><p><strong>Results: </strong>Data from selected ENNS participants revealed AMY1 CNV ranging from 6 to 18 copies. Higher rice intake was significantly associated with increased AMY1 CNV (p = 0.035). Lower AMY1 CNV was more prevalent among overweight and obese individuals.</p><p><strong>Conclusion: </strong>Findings highlight gene-diet interactions and support the relevance of personalized nutrition approaches in the Philippines.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":" ","pages":"23-30"},"PeriodicalIF":1.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12779283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145635031","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":"Gene-Environment Interactions in Celiac Disease: The Role of the Intestinal Epithelium.","authors":"Sara Rahmani, Xavier Mas-Orea, Fernando G Chirdo, Elena F Verdu","doi":"10.1159/000551888","DOIUrl":"10.1159/000551888","url":null,"abstract":"<p><strong>Background: </strong>Celiac disease (CeD) is a chronic, immune-mediated condition driven by dietary gluten in genetically predisposed individuals, primarily those carrying HLA-DQ2 and HLA-DQ8. Unlike other autoimmune diseases, CeD offers an exceptional degree of mechanistic clarity, stemming from the identification of the main environmental driver, gluten, and its link with genetic susceptibility.</p><p><strong>Summary: </strong>While gluten and HLA genotype are necessary for developing CeD, they are not sufficient. Emerging research highlights that environmental and lifestyle factors, including early-life ecosystem, infections, and gut microbiota, critically modulate CeD risk and severity. This review synthesizes emerging insights and focuses on the role of the intestinal epithelium not just as target of immune-mediated injury but as an active interface integrating genetic susceptibility with environmental cues. Recent data reveal that intestinal epithelial cells can release tissue transglutaminase 2 that modifies gluten peptide antigenicity, participate in antigen presentation and immune signaling, and respond to microbial and dietary factors, positioning them as contributors to CeD initiation and progression. The review also highlights knowledge gaps and areas of active debate in CeD.</p><p><strong>Key messages: </strong>CeD has a main environmental driver (gluten) and a defined genetic susceptibility, linked to major histocompatibility complex class II DQ2 and DQ8. Activation of the CD4+ T-cell response by gluten and cytotoxic transformation of intraepithelial lymphocytes culminate in villus atrophy of the proximal small intestine. In this opinion-based perspective, we integrate and review recent evidence suggesting the intestinal epithelium plays an active role in CeD initiation and/or progression, which could lead to strategies to prevent or better treat this condition.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":" ","pages":"101-115"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13290135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147690944","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":"Klotho, Kidneys, and Micronutrient Signaling: A Promising Paradigm for Healthy Aging.","authors":"Sara Mahdavi","doi":"10.1159/000548666","DOIUrl":"10.1159/000548666","url":null,"abstract":"<p><strong>Background: </strong>Klotho, a transmembrane protein with pleiotropic antiaging 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, cardiovascular disease, neurodegeneration, and metabolic dysfunction.</p><p><strong>Summary: </strong>Klotho expression is modifiable through diet, in preclinical and observational studies, 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.</p><p><strong>Key messages: </strong>Klotho emerges as a potential modifiable determinant with 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. Opportunities and limitations of soluble Klotho as a multifaceted biomarker of human health and longevity are highlighted.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":" ","pages":"31-41"},"PeriodicalIF":1.4,"publicationDate":"2026-01-01","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":"Gene Expression Profiling of Peripheral Blood and Endometrial Cancer Risk Factors: Systems Epidemiology Approach in the NOWAC Postgenome Cohort Study.","authors":"Oxana Gavriluk, Igor Snapkow, Jean-Christophe Thalabard, Lars Holden, Marit Holden, Hege M Bøvelstad, Eiliv Lund","doi":"10.1159/000550409","DOIUrl":"10.1159/000550409","url":null,"abstract":"<p><strong>Introduction: </strong>The increasing incidence of endometrial cancer (EC) requires an extensive search for novel preventive tools and early intervention approaches. However, the development of reliable predictive models is impossible without knowledge of genetic alterations prior to diagnosis. In this work, we aimed to establish whether known EC risk factors are associated with peripheral blood gene expression changes in a prospective design and whether such associations differ between women who later developed EC and matched controls.</p><p><strong>Methods: </strong>First, we selected variables (parity status, lifetime number of years of menstruation, coffee consumption, body mass index (BMI), age at menopause, use of oral contraceptives) that were shown to have an impact on EC risk in a large prospective cohort (165,000 women). Next, using BeadChip microarray technology, we tested the association between these variables and gene expression profiles in RNA extracted from mixed circulating immune cells in a nested case-control study (79 case-control pairs) of women from the NOWAC postgenome cohort. Lastly, we undertook a gene set enrichment analysis (GSEA).</p><p><strong>Results: </strong>At overall gene expression level, we found no difference between the EC cases and controls. The introduction of parity status into the statistical model revealed changes in the expression of 1,379 genes in the controls, while we did not observe any expression changes in the cases. Twenty-seven genes were associated with BMI increase in the controls, whereas there was no association observed between changes in BMI and gene expression in women with EC. In GSEA, 2,407 significantly enriched gene sets were attributed to a parity increase among cancer-free women.</p><p><strong>Conclusion: </strong>In this study, we found that an increased number of parities has a life-long effect on the gene expression profile in the peripheral blood of women who never developed cancer. In contrast, in women who were diagnosed with EC later in life, neither multiparity nor elevated BMI showed a significant association with gene expression patterns. However, given the modest sample size and exploratory nature of the study, these findings should be verified in larger cohorts.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":" ","pages":"83-93"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13046301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147317510","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":"Inflammatory Proteins Mediate the Causal Association between Sleep Traits and Breast Cancer: A Mendelian Randomization Study.","authors":"Jiawei Zhou, Lijun Mao","doi":"10.1159/000550315","DOIUrl":"10.1159/000550315","url":null,"abstract":"<p><strong>Introduction: </strong>Breast cancer (BC) is the most frequent cancer in women, driven by a combination of genetic, environmental, and lifestyle factors. Whether modifiable sleep behaviors causally affect BC risk remains unclear. Aims of the study were to systematically assess the causal impact of sleep-related phenotypes on overall BC and its major subtypes using two-sample mendelian randomization (MR) and to determine whether inflammatory proteins mediate these relationships.</p><p><strong>Methods: </strong>Inverse variance weighted served as the main analysis, with sensitivity and reverse-MR analyses as supporting checks. Mediation was quantified with a two-step MR design.</p><p><strong>Results: </strong>Morning chronotype significantly reduced the risk of overall BC (OR = 0.936, 95% CI: 0.893-0.980) and luminal A subtype (OR = 0.944, 95% CI: 0.894-0.996). Short sleep duration was associated with decreased risk of overall BC (OR = 0.482, 95% CI: 0.284-0.818) and luminal A subtype (OR = 0.385, 95% CI: 0.194-0.766), whereas long sleep duration increased the risk of triple-negative BC (OR = 9.433, 95% CI: 2.419-36.775) and luminal A subtype (OR = 2.186, 95% CI: 1.111-4.302). Mediation analysis indicated that CXCL11 accounted for 22.4% of the total causal effect of short sleep duration on luminal A BC.</p><p><strong>Conclusion: </strong>Morning chronotype confers protection against BC, whereas prolonged sleep duration elevates the risk of triple-negative and luminal A BC. CXCL11 mediates part of the protective effect of short sleep on luminal A BC. These findings provide evidence-based support for BC prevention strategies focusing on sleep optimization.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":" ","pages":"63-75"},"PeriodicalIF":2.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12923251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145966395","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":"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":"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":"10.1159/000548169","url":null,"abstract":"<p><strong>Introduction: </strong>The prevalence of gout, a chronic metabolic disease, has recently increased. Polygenic risk scores (PRSs) represent a useful tool for predicting patient outcomes of this condition. However, the clinical utility of PRS in disease prediction remains controversial.</p><p><strong>Methods: </strong>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 ML contexts), random forest (RF), decision tree, extreme gradient boosting, and light gradient boosting.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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":"142-151"},"PeriodicalIF":1.4,"publicationDate":"2025-01-01","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":"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}