Lifestyle Genomics最新文献

Introduction: 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 one week.

Methods: 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 one 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.

Results: The cohort of 35 persons was 43% female, aged 18 to 70 y, with BMI between 26.4 to 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 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 (MUFA) (p = 0.0078). These interactions were not statistically significant at the end of the LF intervention.

Conclusion: Our findings suggest that the Mediterranean diet has stronger influence on regulating lipid factors in individuals with the CC genotype at TCF7L2 variant rs7903146. This diet-genotype interaction may have significant implications for understanding the inter-individual variation of metabolic response on specific dietary regimens.

Introduction: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia worldwide. Although catheter ablation is the most efficacious therapy, relapses occur frequently (30%) in the first year after ablation. Novel biomarkers of recurrence are needed for a better prediction of recurrence and management of AF. In this pilot study, we aimed to analyze the baseline proteome of subjects included in a case-control study to find differential proteins associated with AF recurrence.

Methods: Baseline serum proteomics (354 proteins) data from 16 cases (recurrent AF) and 17 controls (non-recurrent) were obtained using MS/MS analysis. False discovery rate was performed using a nonlinear fitting method for the selection of proteins. Logistic regression models were used to further analyze the association between differentially expressed proteins and AF recurrence Results: Ten proteins were differentially represented in cases vs controls. Two were upregulated in the cases compared to the controls: keratin type I cytoskeletal 17 (FC=2.14; p=0.017) and endoplasmic bifunctional protein (Fold-change [FC]=1.65; p=0.032). And eight were downregulated in the cases compared to the controls: C4bpA (FC=0.64; p=0.006), coagulation factor XI (FC=0.83; p=0.011), CLIC1 (FC=0.62; p=0.017), haptoglobin (FC=0.37; p=0.021), Ig alpha-2 chain C region (FC=0.49; p=0.022), C4bpB (FC=0.73; p=0.028), N-acetylglucosamine-1-phosphotransferase subunit gamma (FC=0.61; p=0.033) and platelet glycoprotein Ib alpha chain (FC=0.84; p=0.038).

Conclusion: This pilot study identifies ten differentially expressed serum proteins associated with AF recurrence, offering potential biomarkers for improved prediction and management.

Introduction: It has been reported that even with the same body mass index (BMI), there are subjects with metabolically healthy or unhealthy phenotype. The main determinants of the unhealthy phenotype are the type and distribution of fat, ectopic fat accumulation, genetics, and lifestyle factors. Uncoupling proteins (UCPs) disengage mitochondrial respiration from ATP synthesis and result in heat production, which in turn is related to energy expenditure and, thus, to fat mass accumulation. The association of the UCP1 -3826A/G (rs1800592), UCP2 Ala55Val (rs660339), and UCP3 -55C/T (rs1800849) variants with metabolic variables was evaluated according to metabolic phenotype in Mexican women.

Methods: Women aged 18 to 65 years classified as normal weight (NW) or excessive weight (EW) according to their BMI (from 18.5 to <25 kg/m2 for NW, and from 25 to <40 kg/m2 for EW), were included. Participants were classified into two metabolic phenotypes: metabolically healthy or metabolically unhealthy (MH or MUH, respectively) based on ATP-III criteria and the homeostasis model assessment of insulin resistance (HOMA-IR). The genetic variants were determined by allelic discrimination using TaqMan® probes.

Results: In participants with the UCP1 -3826A/G variant, an increased risk of hypercholesterolemia was observed in those with the NW-MUH phenotype (OR=5.09, CI=1.03-25.12, p=0.017). The UCP2 Ala55Val variant in EW-MUH subjects was associated with higher abdominal obesity risk (OR=3.23, CI=1.21-8.60, p=0.019), while no associations were found with the UCP3 -55C/T variant.

Conclusion: UCP1 and UCP2 variants are related with hypercholesterolemia and visceral fat accumulation in women with MUH phenotype.

Introduction: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

Introduction: Preterm birth (PTB) is associated with newborn morbidity and mortality. DNA methylation plays an important role in the development of fetus, thus can also serve as an epigenetic biomarker. Limited epigenetic studies were conducted in regard to PTB. Thus, this study aims to determine whether there are any epigenetic changes amongst PTB vs. term birth (TB).

Methods: In the current study, a total 218 cord blood samples from three different PTB studies have been carried out to explore differentially methylated sites (DMS) and regions (DMRs) associated with PTB. The differential methylation analysis was done after controlling for multiple covariates like age, gender, and disease status. The DMRs (genes and promoters) and DMS (CpG) were investigated in PTB compared to TB infants.

Results: In PTB infants, genes like RNASE3, HGF, CLEC5A, LIPN, NXF1, and CCDC12 showed hypermethylation (p < 0.05) while the MUC20 and IFNL4 genes showed hypomethylation (p < 0.05) along with other significantly identified genes in this analysis. The eForge analysis of hypermethylated (p < 0.05) CpG sites exhibited enrichment in different fetal tissues like small and large intestine, adrenal gland, fetal heart, lungs, and kidney while hypomethylated CpGs showed no significant enrichment. The GO enrichment analysis of these genes revealed pathways associated with the regulation of immune response. Interestingly, the analysis also observed S100A9 and S100A8 genes, along with their associated CpG sites exhibited hypermethylation (p < 0.05) in PTB infants which plays a crucial role in developing neonatal sepsis.

Conclusion: Overall, this study revealed differential methylation in immune-related genes related to PTB that could be used as potential epigenetics biomarkers. These findings not only enhance our understanding of PTB pathogenesis but also pave the way for developing innovative diagnostic and therapeutic strategies.

Background: Precision nutrition is based on the integration of individual's phenotypical and biological characteristics including genetic variants, epigenetic marks, gut microbiota profiles, and metabolite fingerprints as well as medical history, lifestyle practices, and environmental and cultural factors. Thus, nutriomics areas including nutrigenomics, nutrigenetics, nutriepigenetics, nutrimetabolomics, and nutrimetagenomics have emerged to comprehensively understand the complex interactions between nutrients, diet, and the human body's molecular processes through precision nutrition.

Summary: This document from the Ibero-American Network of Nutriomics and Precision Nutrition (RINN22; https://rinn22.com/) provides a comprehensive overview of the concepts of precision nutrition approaches to guide their application in clinical and public health as well as establish the position of RINN22 regarding the current and future state of precision nutrition.

Key messages: The progress and participation of nutriomics to precision nutrition is an essential pillar for addressing diet-related diseases and developing innovative managing strategies, which will be promoted by advances in bioinformatics, machine learning, and integrative software, as well as the description of specific novel biomarkers. In this context, synthesizing and critically evaluating the latest developments, potential applications, and future needs in the field of nutrition is necessary with a holistic perspective, incorporating progress in omics technologies aimed at precision nutrition interventions. This approach must address and confront healthy, social, food security, physically active lifestyle, sanitation, and sustainability challenges with preventive, participatory, and predictive strategies of personalized, population, and planetary nutrition for a precision tailored health.

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.

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: 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.