Lifestyle Genomics最新文献

{"title":"The Molecular Basis of Olfactory Dysfunction in COVID-19 and Long COVID.","authors":"Cleo Anastassopoulou, Nikolaos Davaris, Stefanos Ferous, Nikolaos Siafakas, Fotini Boufidou, Konstantinos Anagnostopoulos, Athanasios Tsakris","doi":"10.1159/000539292","DOIUrl":"10.1159/000539292","url":null,"abstract":"<p><p>Olfactory dysfunction (OD) is not uncommon following viral infection. Herein, we explore the interplay of host genetics with viral correlates in coronavirus disease 2019 (COVID-19)- and long COVID-related OD, and its diagnosis and treatment that remain challenging. Two genes associated with olfaction, UGT2A1 and UGT2A2, appear to be involved in COVID-19-related anosmia, a hallmark symptom of acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), particularly in the early stages of the pandemic. SARS-CoV-2 infects olfactory support cells, sustentacular and Bowman gland cells, that surround olfactory sensory neurons (OSNs) in the olfactory epithelium (OE) where the initial step of odor detection takes place. Anosmia primarily arises from the infection of support cells of the OE, followed by the deciliation and disruption of OE integrity, typically without OSN infection. Through the projected axons of OSNs, the virus could theoretically reach the olfactory bulb and brain, but current evidence points against this route. Intriguingly, SARS-CoV-2 infection of support cells leads to profound alterations in the nuclear architecture of OSNs, leading to the downregulation of odorant receptor-related genes, e.g., of Adcy3. Viral factors associated with the development of OD include spike protein aminoacidic changes, e.g., D614G, the first substitution that was selected early during SARS-CoV-2 evolution. More recent variants of the Omicron family are less likely to cause OD compared to Delta or Alpha, although OD has been associated with a milder disease course. OD is one of the most prevalent post-acute neurologic symptoms of SARS-CoV-2 infection. The tens of millions of people worldwide who have lingering problems with OD wait eagerly for effective new treatments that will restore their sense of smell which adds value to their quality of life.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":" ","pages":"42-56"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945189","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":"Acute Administration of Calafate (Berberis microphylla) Extract Induces the Expression of Thermogenic Markers and Modulates Gut Microbiota in Mice Fed a High-Fat Chow Diet.","authors":"Lissette Duarte, Vanessa Villanueva, Robert Barroux, Juan Francisco Orellana, Carlos Poblete-Aro, Martin Gotteland, Mauricio Castro, Fabien Magne, Diego F Garcia-Diaz","doi":"10.1159/000539881","DOIUrl":"10.1159/000539881","url":null,"abstract":"<p><strong>Introduction: </strong>Obesity, characterized by excess adipose tissue, is a major public health problem worldwide. Brown adipose tissue (BAT) and beige adipose tissue participate in thermogenesis through uncoupling protein 1 (UCP1). Polyphenols including those from Calafate (a native polyphenol-rich Patagonian berry), are considered as potential anti-obesity compounds due to their pro-thermogenic characteristics. However, polyphenols are mainly metabolized by the gut microbiota (GM) that may influence their bioactivity and bioavailability. The aim of this study was to determine the impact of dietary administration with a Calafate polyphenol-rich extract on thermogenic activity of BAT and beige adipose tissue and GM composition.</p><p><strong>Methods: </strong>Eight-week-old C57BL6 mice (n = 30) were divided into 4 groups to receive for 24 weeks a control diet (C), a high-fat diet alone (HF), or high-fat diet supplemented with Calafate extract (HFC) or the same high-fat diet supplemented with Calafate extract but treated with antibiotics (HFCAB) from week 19-20. Administration with Calafate extract (50 mg/kg per day) was carried out for 3 weeks from week 21-23 in the HFC and HFCAB groups. After euthanasia, gene expression of thermogenic markers was analyzed in BAT and inguinal white adipose tissue (iWAT). Transmission electron microscopy was performed to assess mitochondrial morphology and cristae density in BAT. GM diversity and composition were characterized by deep sequencing with the MiSeq Illumina platform.</p><p><strong>Results: </strong>Calafate extract administration had no effect on weight gain in mice fed a high-fat diet. However, it prevented alterations in mitochondrial cristae induced by HFD and increased Dio2 expression in BAT and iWAT. The intervention also influenced the GM composition, preventing changes in specific bacterial taxa induced by the high-fat diet. However, the antibiotic treatment prevented in part these effects, suggesting the implications of GM.</p><p><strong>Conclusion: </strong>These results suggest that the acute administration of a Calafate extract modulates the expression of thermogenic markers, prevents alterations in mitochondrial cristae and intestinal microbiota in preclinical models. The study highlights the complex interaction between polyphenols, thermogenesis, and the GM, providing valuable insights into their potential roles in the treatment of obesity-related metabolic diseases.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":" ","pages":"72-81"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419731","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":"17th ISNN Congress, 5-7 December 2024, Juhu, Mumbai, India: Precision Nutrition in Nutritional Deficiencies & Optimal Health.","authors":"Louis Pérusse","doi":"10.1159/000542462","DOIUrl":"https://doi.org/10.1159/000542462","url":null,"abstract":"","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":"17 1","pages":"136-150"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716405","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":"Impact of the rs822393 Variant on Adiponectin Levels and Metabolic Parameters after Weight Loss Secondary to a High-Fat Hypocaloric Diet with Mediterranean Pattern.","authors":"David Primo, Olatz Izaola, Juan Jose Lopez Gomez, Daniel Rico, Daniel A de Luis","doi":"10.1159/000539056","DOIUrl":"10.1159/000539056","url":null,"abstract":"<p><strong>Introduction: </strong>The effects of the rs822393 variant of ADIPOQ gene on metabolic parameters such as insulin resistance and adiponectin levels following weight loss through dietary intervention are still uncertain. The aim of this study was to evaluate the role of rs822393 of ADIPOQ gene on adiponectin levels and metabolic parameters after weight loss with a high-fat hypocaloric diet with Mediterranean pattern during 12 weeks.</p><p><strong>Methods: </strong>A population of 283 patients with obesity was allocated to a dietary intervention trial with a high-fat hypocaloric diet during 12 weeks. Adiposity and biochemical parameters were determined. rs822393 was assessed with a dominant model analysis (CC vs. CT + TT).</p><p><strong>Results: </strong>These patients had three different genotypes: CC (59.0%), CT (33.6%), and TT (7.4%). The allelic frequencies for C and T were 0.89 and 0.20, respectively. Basal and post-intervention HDL cholesterol, adiponectin levels, and adiponectin/leptin ratio were lower in T-allele than non-T-allele carriers. After dietary intervention, BMI, weight, fat mass, waist circumference, systolic blood pressure, insulin, HOMA-IR, leptin, total cholesterol, and LDL cholesterol levels improved significantly in both genotype groups. Moreover, HDL cholesterol (CC vs. CT + TT) (delta: 8.9 ± 1.1 mg/dL vs. 1.7 ± 0.8 mg/dL; p = 0.02), serum adiponectin in non-T-allele carriers (43.1 ± 5.9 ng/dL vs. 2.8 ± 3 0.0 ng/dL; p = 0.01), and adiponectin/leptin ratio (1.37 ± 0.1 units vs. 0.17 ± 0.08 units; p = 0.02) improved only in non-T-allele carriers after weight loss.</p><p><strong>Conclusion: </strong>Individuals with obesity and without the T allele of rs822393 experienced improvements in adiponectin levels, adiponectin/leptin ratio, and HDL cholesterol levels after following a high-fat hypocaloric diet with a Mediterranean pattern.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":" ","pages":"64-71"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310993","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":"Barriers in Translating Existing Nutrigenetics Insights to Precision Nutrition for Cardiometabolic Health in Ethnically Diverse Populations.","authors":"Ramatu Wuni, Karani Santhanakrishnan Vimaleswaran","doi":"10.1159/000541909","DOIUrl":"10.1159/000541909","url":null,"abstract":"<p><strong>Background: </strong>Cardiometabolic diseases pose a significant threat to global public health, with a substantial majority of cardiovascular disease mortality (more than three-quarters) occurring in low- and middle-income countries. There have been remarkable advances in recent years in identifying genetic variants that alter disease susceptibility by interacting with dietary factors. Despite the remarkable progress, several factors need to be considered before the translation of nutrigenetics insights to personalised and precision nutrition in ethnically diverse populations. Some of these factors include variations in genetic predispositions, cultural and lifestyle factors as well as socio-economic factors.</p><p><strong>Summary: </strong>This review aimed to explore the factors that need to be considered in bridging the gap between existing nutrigenetics insights and the implementation of personalised and precision nutrition across diverse ethnicities. Several factors might influence variations among individuals with regard to dietary exposures and metabolic responses, and these include genetic diversity, cultural and lifestyle factors as well as socio-economic factors. A multi-omics approach involving disciplines such as metabolomics, epigenetics, and the gut microbiome might contribute to improved understanding of the underlying mechanisms of gene-diet interactions and the implementation of precision nutrition although more research is needed to confirm the practicality and effectiveness of this approach. Conducting gene-diet interaction studies in diverse populations is essential and studies utilising large sample sizes are required as this improves the power to detect interactions with minimal effect sizes. Future studies should focus on replicating initial findings to enhance reliability and promote comparison across studies. Once findings have been replicated in independent samples, dietary intervention studies will be required to further strengthen the evidence and facilitate their application in clinical practice.</p><p><strong>Key messages: </strong>Nutrigenetics has a potential role to play in the prevention and management of cardiometabolic diseases. Conducting gene-diet interaction studies in diverse populations is essential giving the genetic diversity and variations in dietary patterns. Integrating data from disciplines such as metabolomics, epigenetics, and the gut microbiome could help in early identification of individuals at risk of cardiometabolic diseases as well as the implementation of precise dietary interventions for preventing and managing cardiometabolic diseases.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":" ","pages":"122-135"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522267","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":"Genetic Influence on Capsaicin Tolerance: Precision Nutrition Implications for Obesity Handling.","authors":"Omar Ramos-Lopez, Yesenia Martinez-Aceviz, Ana Alondra Sobrevilla-Navarro, Jose Roman Chavez-Mendez","doi":"10.1159/000539293","DOIUrl":"10.1159/000539293","url":null,"abstract":"<p><strong>Introduction: </strong>It has been suggested that capsaicin (CAP), a major pungent component in chili peppers, can be used as an anti-obesity ingredient due to effects on energy metabolism, but evidence is not consistent. Genetics may account for differences in CAP tolerance and its impact on adiposity status. The aim of this study was to systematically review current evidence concerning the role of genetic polymorphisms influencing CAP tolerance.</p><p><strong>Methods: </strong>The present systematic review analyzed and synthesized available evidence concerning associations between genetic polymorphisms and CAP tolerance following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) guidelines. Databases such as PubMed/MEDLINE, Cochrane, Scopus, Google Scholar, SciELO, and LILACS were screened. Out of 228 publications identified, only 6 meet inclusion criteria and were finally included in the final report.</p><p><strong>Results: </strong>Overall, a total of 28 single nucleotide polymorphisms were associated with several CAP tolerance traits including sensitivity to burning/stinging, heat pain, and cough reactions, and detection of bitter taste thresholds. These genetic variants were located within 6 genes involved in key physiological processes such synthesis of tetrahydrobiopterin and nitric oxide production (GCH1), CAP uptake and transduction of thermal stimuli (TRPV1), and bitter taste perception (TAS2R38, TAS2R3, TAS2R4, and TAS2R5).</p><p><strong>Conclusion: </strong>There is evidence about the influence of genetic polymorphisms on CAP tolerance by affecting nociceptive signaling, CAP binding, and bitter tasting. This knowledge may facilitate the design and implementation of innovative CAP-based nutrigenetic strategies for a more precise clinical management of obesity.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":" ","pages":"57-63"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141175484","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":"Precision Nutrition for Management of Cardiovascular Disease Risk during Menopause.","authors":"Hannah E Cabre, Emily K Woolf, Leanne M Redman","doi":"10.1159/000540337","DOIUrl":"10.1159/000540337","url":null,"abstract":"<p><strong>Background: </strong>Women can spend up to 40% of their lives in the postmenopausal state. As women begin to transition into menopause, known as perimenopause, changes in hormonal concentrations and body composition dramatically increase overall cardiometabolic risk. Dietary patterns and interventions can be utilized to prevent and treat cardiovascular disease (CVD) and some dietary patterns over others may be more beneficial due to their specific effects on the health aspects of menopause. In this narrative review, we summarize key cardiovascular alterations that occur during the menopause transition and explore current dietary recommendations to address CVD risk as well as explore the new frontier of precision nutrition and the implications for nutrition prescription during menopause.</p><p><strong>Summary: </strong>Popular dietary interventions for CVD such as the Dietary Approaches to Stop Hypertension (DASH) diet and the Mediterranean diet (MED) have limited data in women following menopause. However, both diets improve CVD risk biomarkers of total cholesterol and low-density lipoprotein cholesterol as well as lower oxidative stress and inflammation and improve endothelial function. As the menopause transition increases the risk for developing metabolic syndrome, insulin insensitivity, and dyslipidemia, the DASH diet and MED may be impactful dietary strategies for mediating CVD risk in menopausal women. However, these are \"one-size-fits-all\" approaches that neglect individual characteristics such as genetic predisposition and environmental factors. Precision nutrition considers individual factors for nutrition prescription, spanning from evaluating food intake preferences and behaviors to deep phenotyping. Data from a large-scale investigation of the menopause transition suggests nutritional strategies that address postprandial glycemic responses, and the gut microbiome may attenuate some of the unfavorable effects of menopause on CVD risk factors.</p><p><strong>Key messages: </strong>Considering menopause, women are a clinical population that would greatly benefit from precision nutrition. Future research should explore the use of machine learning and artificial intelligence in a precision nutrition framework to modify the DASH diet and MED to address adverse effects that occur during the menopause transition are vital for supporting women's health as they age.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":" ","pages":"93-101"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11394930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759588","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":"Nutriomic Effects of Precision Lipids on Murine Hepatic Triacylglycerol Alterations Induced by High-Fat Diets.","authors":"Ana Clara Fariña, Jimena Verónica Lavandera, Luciana Vera Candioti, Candela Luján Suppo, Claudio Adrián Bernal","doi":"10.1159/000539077","DOIUrl":"10.1159/000539077","url":null,"abstract":"<p><strong>Introduction: </strong>This study aims to investigate if a mixture of functional lipids (FLs), containing conjugated linoleic acid (CLA), tocopherols (TPs), and phytosterols (PSs), prevents some lipid alterations induced by high-fat (HF) diets, without adverse effects.</p><p><strong>Methods: </strong>Male CF1 mice (n = 6/group) were fed (4 weeks) with control (C), HF, or HF + FL diets.</p><p><strong>Results: </strong>FL prevented the overweight induced by the HF diet and reduced the adipose tissue (AT) weight, associated with lower energy efficiency. After the intervention period, the serum triacylglycerol (TAG) levels in both HF diets underwent a decrease associated with an enhanced LPL activity (mainly in muscle). The beneficial effect of the FL mixture on body weight gain and AT weight might be attributed to the decreased lipogenesis, denoted by the lower mRNA levels of SREBP1-c and ACC in AT, as well as by an exacerbated lipid catabolism, reflected by increased mRNA levels of PPARα, ATGL, HSL, and UCP2 in AT. Liver TAG levels were reduced in the HF + FL group due to an elevated lipid oxidation associated with a higher CPT-1 activity and mRNA levels of PPARα and CPT-1a. Moreover, genes linked to fatty acid biosynthesis (SREBP1-c and ACC) showed decreased mRNA levels in both HF diets, this finding being more pronounced in the HF + FL group.</p><p><strong>Conclusion: </strong>The administration of an FL mixture (CLA + TP + PS) prevented some lipid alterations induced by a HF diet, avoiding frequent deleterious effects of CLA in mice through the modulation of gene expression related to the regulation of lipid metabolism.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":" ","pages":"82-92"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476913","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":"Interplay of Large Neutral Amino Acids, Metabolic Syndrome, and Apolipoprotein E ε4 on Brain Integrity at Midlife.","authors":"Cherry Youn, Marie L Caillaud, Yanrong Li, Isabelle Gallagher, Barbara Strasser, Hirofumi Tanaka, Andreana P Haley","doi":"10.1159/000540336","DOIUrl":"10.1159/000540336","url":null,"abstract":"<p><strong>Introduction: </strong>Large neutral amino acids (LNAAs) tryptophan and phenylalanine have been implicated in the pathogenesis of neurodegenerative diseases. Given limited research on the effects of LNAA on brain health across different life stages, vascular risk, and genetic backgrounds, our study aimed to explore the interaction of LNAA levels, metabolic syndrome (MetS), and the presence of the apolipoprotein E ε4 (ApoE ε4) allele brain integrity at midlife.</p><p><strong>Methods: </strong>Sixty-eight adults aged 40-61 underwent a health assessment to calculate the number of MetS components, quantify LNAA, measure white matter hyperintensity (WMH) volume, and genotype ApoE ε4. Multivariate linear regression analyses were performed to test the joint effect of LNAA, MetS, and ApoE ε4 on WMH while adjusting for sex, age, and education.</p><p><strong>Results: </strong>Significant 3-way interactions were observed between serum tryptophan (β = 0.042, SE = 0.018, p &lt; 0.05) and phenylalanine (β = 0.044, SE = 0.013, p &lt; 0.01) levels, number of MetS components, and ApoE ε4 alleles status on WMH volume. Neither individual LNAA levels nor MetS components alone predicted WMH volume.</p><p><strong>Conclusions: </strong>The study highlights significant 3-way interactions between LNAA, MetS, and genetic risk factors in the pathology of WMH, particularly in individuals genetically predisposed to Alzheimer's disease. These interactions suggest differential impacts of LNAA on WMH volume dependent on both genetic and metabolic factors. Results emphasize the need for personalized metabolic and genetic profile assessments in neurodegenerative disease management.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":" ","pages":"113-121"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11385466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893770","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":"Are Carriers Unaffected? A Literature Review of Metabolic and Health Outcomes among Genetic Carriers of Phenylketonuria.","authors":"Sophia M Khan, Robyn R Heister, Justine R Keathley","doi":"10.1159/000540549","DOIUrl":"10.1159/000540549","url":null,"abstract":"<p><strong>Background: </strong>Phenylketonuria (PKU) is an autosomal recessive genetic condition that results in reduced enzymatic functioning within the phenylalanine hydroxylase (PAH) pathway, which is involved in the metabolism of phenylalanine (Phe) into tyrosine (Tyr). Without dietary intervention, individuals with PKU exhibit significantly elevated levels of Phe, which is presumed to cause severe neurological dysfunction and other associated health risks. Carriers of PKU are heterozygotes for a PAH gene mutation and are typically described in the literature as \"unaffected.\" However, decades of existing research challenges this classical thinking and it is plausible that these individuals currently classified as carriers may present with an intermediate phenotype or may be \"moderately affected.\"</p><p><strong>Summary: </strong>The purpose of this scoping review was to explore this hypothesis further, by searching for and summarizing existing literature on metabolism and health outcomes among PKU carriers. Preliminary research has suggested that some PKU carriers exhibit reduced PAH enzyme function, and relatedly, elevated circulating Phe levels compared to noncarriers. In addition, Phe dosing trials have further demonstrated that carriers have increased Phe levels and decreased Tyr levels compared to noncarriers. Because of these metabolic perturbations, it is biologically plausible for carriers to experience an intermediate phenotype in terms of metabolic consequences and clinical outcomes. While these outcomes have yet to be thoroughly explored, early research has found associations between PKU carrier status and lower IQs as well as decreased executive functioning, memory, processing speed, and inhibitory control. The PAH pathway is also involved in melanogenesis, and research has demonstrated increased melanoma risk among PKU carriers. However, there are many limitations to this research, and thus whether or not carriers are clinically impacted cannot yet be conclusively determined.</p><p><strong>Key message: </strong>Overall, while preliminary research suggests a possible intermediate phenotype among PKU carriers, the current available research is limited and PKU carriers are still clinically considered \"unaffected.\" This review outlines the current literature while discussing future research endeavors related to the metabolism and health of PKU carriers.</p>","PeriodicalId":18030,"journal":{"name":"Lifestyle Genomics","volume":" ","pages":"102-112"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855861","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}