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Gene-Nutrient Interactions

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (30 April 2015) | Viewed by 100953

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Dr. Lu Qi

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1. Department of Nutrition, Harvard School of Public Health, Boston, MA, USA
2. Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
Interests: genetic; gene-environment interaction; nutrition; epidemiology; obesity; diabetes; cardiovascular disease

Special Issue Information

Dear Colleagues,

This special issue is intended to present feature and scholarly papers that address some of the diverse array of topics related to Gene-Nutrient Interaction. These topics include but are not limited to epidemiological (population-based studies, clinical trials) and experimental (animal, cellular, and functional) studies with a focus on interactions between genetic variants and dietary factors such as nutrients, foods, and dietary patterns in relation to human health such as various chronic diseases, metabolic changes, and aging. Research in other omics such as transcriptomics, epigenomics, metabolomics, and proteomics, as well as investigations on microbiome that are closely related to gene-nutrient interactions would be also included. We invite scientists and researchers from all these relevant fields to submit papers for this important special issue. Original research studies and reviews on all the topics related to gene-nutrient interaction are invited.

Dr. Lu Qi
Guest Editors

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Keywords

genetic
nutrients
gene-diet interaction
chronic diseases
personalized nutrition

Published Papers (12 papers)

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1366 KiB

Open AccessArticle

Differential DNA Methylation in Relation to Age and Health Risks of Obesity

by María Luisa Mansego, Fermín I. Milagro, María Ángeles Zulet, María J. Moreno-Aliaga and José Alfredo Martínez

Int. J. Mol. Sci. 2015, 16(8), 16816-16832; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms160816816 - 24 Jul 2015

Cited by 40 | Viewed by 7546

Abstract

The aim of this study was to evaluate whether genome-wide levels of DNA methylation are associated with age and the health risks of obesity (HRO); defined according to BMI categories as “Low HRO” (overweight and class 1 obesity) versus “High HRO” (class 2 and class 3 obesity). Anthropometric measurements were assessed in a subsample of 48 volunteers from the Metabolic Syndrome Reduction in Navarra (RESMENA) study and 24 women from another independent study, Effects of Lipoic Acid and Eicosapentaenoic Acid in Human Obesity (OBEPALIP study). In the pooled population; the methylation levels of 55 CpG sites were significantly associated with age after Benjamini-Hochberg correction. In addition, DNA methylation of three CpG sites located in ELOVL2; HOXC4 and PI4KB were further negatively associated with their mRNA levels. Although no differentially methylated CpG sites were identified in relation to HRO after multiple testing correction; several nominally significant CpG sites were identified in genes related to insulin signaling; energy and lipid metabolism. Moreover, statistically significant associations between BMI or mRNA levels and two HRO-related CpG sites located in GPR133 and ITGB5 are reported. As a conclusion, these findings from two Spanish cohorts add knowledge about the important role of DNA methylation in the age-related regulation of gene expression. In addition; a relevant influence of age on DNA methylation in white blood cells was found, as well as, on a trend level, novel associations between DNA methylation and obesity. Full article

(This article belongs to the Special Issue Gene-Nutrient Interactions)

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Open AccessArticle

Gene-Diet Interaction between SIRT6 and Soybean Intake for Different Levels of Pulse Wave Velocity

by Kexin Sun, Xiao Xiang, Na Li, Shaoping Huang, Xueying Qin, Yiqun Wu, Xun Tang, Pei Gao, Jing Li, Tao Wu, Dafang Chen and Yonghua Hu

Int. J. Mol. Sci. 2015, 16(7), 14338-14352; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms160714338 - 24 Jun 2015

Cited by 5 | Viewed by 5414

Abstract

Soybean is a common food for the Chinese people. We aimed to investigate the risk for brachial ankle pulse wave velocity (baPWV) with inflammatory-related SNPs and soybean. baPWV was measured, and 16 inflammatory-related SNPs located on ADIPOQ, CDH13, SIRT3, SIRT6, CXCL12, CXCR4, NOS1, PON1 and CDKN2B were genotyped in 1749 Chinese participants recruited from various communities. ADIPOQ rs12495941 (GT/TT vs. GG: crude OR = 1.27, p = 0.044) and SIRT6 rs107251 (CT/TT vs. CC: crude OR = 0.74, p = 0.009) were associated with abnormal baPWV (baPWV ≥ 1700 cm/s). After adjustment for conventional environmental risk factors, rs12495941 was associated with abnormal baPWV (GT/TT vs. GG: adjusted OR = 1.43, p = 0.011), but the association between rs107251 and abnormal baPWV was not significant (CT/TT vs. CC: adjusted OR = 0.83, p = 0.173). The interaction between rs107251 and soybean intake for different levels of baPWV was statistically significant (p = 0.017). Compared with a high level of soybean intake, a low level of soybean intake can significantly decrease the risk of abnormal baPWV in individuals of rs107251 CT/TT genotypes (≤100 vs. >100 g/week: adjusted OR = 0.542, p = 0.003). In this study, associations between ADIPOQ rs12495941, SIRT6 rs107251 and baPWV, as well as an interaction between SIRT6 rs107251 and soybean intake for different levels of baPWV were found. Full article

(This article belongs to the Special Issue Gene-Nutrient Interactions)

809 KiB

Open AccessArticle

Effect of Dose and Administration Period of Seed Cake of Genetically Modified and Non-Modified Flax on Selected Antioxidative Activities in Rats

by Magdalena Matusiewicz, Iwona Kosieradzka, Magdalena Zuk and Jan Szopa

Int. J. Mol. Sci. 2015, 16(6), 14259-14275; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms160614259 - 23 Jun 2015

Cited by 14 | Viewed by 6959

Abstract

Flaxseed cake containing antioxidants is a valuable dietary component. Its nutritional effect may be diminished by the presence of anti-nutrients. The work was aimed at determining the effect of different contents of flaxseed cake in diets and their administration period on the development of rats and selected parameters of their health status. Diets with 15% and 30% addition of genetically modified (GM) flax seed cake with enhanced synthesis of polyphenols, as well as Linola non-GM flax were administered in short-term (33 days) and long-term (90 days) experiments. The 30% addition of flaxseed cake reduced digestibility of dietary nutrients, GM flaxseed cake lowered body weight gains. The relative weight of selected organs, hematological blood markers and serum activities of aspartate and alanine aminotransferases (AST, ALT) were not affected. Flaxseed cake consumption reduced serum concentration of albumins and increased globulins. Administration of 30% flaxseed cake improved plasma total antioxidant status and 30% GM flaxseed cake lowered liver thiobarbituric acid reactive substances. The activities of superoxide dismutase in erythrocytes, glutathione peroxidase in plasma and the liver concentration of 8-oxo-2′-deoxyguanosine were not changed. Most morphometric parameters of the small intestine did not differ between feeding groups. The administration of diets with 30% addition of flaxseed cake for 90 days improved the antioxidant status in rats. Full article

(This article belongs to the Special Issue Gene-Nutrient Interactions)

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Open AccessArticle

25-Hydroxyvitamin D₃ Levels, BsmI Polymorphism and Insulin Resistance in Brazilian Amazonian Children

by Fernanda Cobayashi, Bárbara Hatzlhoffer Lourenço and Marly Augusto Cardoso

Int. J. Mol. Sci. 2015, 16(6), 12531-12546; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms160612531 - 03 Jun 2015

Cited by 29 | Viewed by 5418

Abstract

Vitamin D is associated with a wide range of other functions beyond bone development. We evaluated the factors associated with 25-hydroxyvitamin D levels in 974 children aged ≤10 years and the impact of BsmI polymorphism of the vitamin D receptor (VDR) gene (rs1544410) on metabolic parameters in a subsample (n: 430) with a follow-up 2 years later from the initial population-based cross-sectional study. Multiple linear regression models were used in the analyses. The prevalence (95% CI) of vitamin D deficiency, insufficiency and sufficiency of children was 11.1% (9.2–13.2), 21.8% (19.2–24.5) and 67.2% (64.1–70.1), respectively. Overall, 23% of the variation in serum 25-hydroxyvitamin D concentrations was accounted for by BsmI polymorphism β = −0.053 (95% CI) (−0.100, −0.006), maternal schooling (≥9 years) β = 0.100 (0.039, 0.161), serum vitamin E β = 0.478 (0.381, 0.574), total cholesterol concentration β = 0.232 (0.072, 0.393) and serum folate β = 0.064 (0.013, 0.115). BsmI polymorphism was positively associated with HOMA-IR β = 0.122 (0.002, 0.243) and fasting glucose concentration β = 1.696 (0.259, 3.133). In conclusion, variables related to socioeconomic level, the presence of the allele risk for BsmI and other nutrient concentrations were associated with serum 25-hydroxyvitamin D concentrations. Our results suggest that BsmI polymorphism is correlated with metabolic outcomes. Full article

(This article belongs to the Special Issue Gene-Nutrient Interactions)

429 KiB

Open AccessArticle

Genome-Wide Expression in Visceral Adipose Tissue from Obese Prepubertal Children

by Concepción M. Aguilera, Carolina Gomez-Llorente, Inés Tofe, Mercedes Gil-Campos, Ramón Cañete and Ángel Gil

Int. J. Mol. Sci. 2015, 16(4), 7723-7737; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms16047723 - 08 Apr 2015

Cited by 52 | Viewed by 6808

Abstract

Characterization of the genes expressed in adipose tissue (AT) is key to understanding the pathogenesis of obesity and to developing treatments for this condition. Our objective was to compare the gene expression in visceral AT (VAT) between obese and normal-weight prepubertal children. A total of fifteen obese and sixteen normal-weight children undergoing abdominal elective surgery were selected. RNA was extracted from VAT biopsies. Microarray experiments were independently performed for each sample (six obese and five normal-weight samples). Validation by quantitative PCR (qPCR) was performed on an additional 10 obese and 10 normal-weight VAT samples. Of 1276 differentially expressed genes (p < 0.05), 245 were more than two-fold higher in obese children than in normal-weight children. As validated by qPCR, expression was upregulated in genes involved in lipid and amino acid metabolism (CES1, NPRR3 and BHMT2), oxidative stress and extracellular matrix regulation (TNMD and NQO1), adipogenesis (CRYAB and AFF1) and inflammation (ANXA1); by contrast, only CALCRL gene expression was confirmed to be downregulated. In conclusion, this study in prepubertal children demonstrates the up- and down-regulation of genes that encode molecules that were previously proposed to influence the pathogenesis of adulthood obesity, as well as previously unreported dysregulated genes that may be candidate genes in the aetiology of obesity. Full article

(This article belongs to the Special Issue Gene-Nutrient Interactions)

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Open AccessArticle

Interactive Effects of Dietary Lipid and Phenotypic Feed Efficiency on the Expression of Nuclear and Mitochondrial Genes Involved in the Mitochondrial Electron Transport Chain in Rainbow Trout

by Jonathan C. Eya, Vitalis O. Ukwuaba, Rodrigue Yossa and Ann L. Gannam

Int. J. Mol. Sci. 2015, 16(4), 7682-7706; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms16047682 - 07 Apr 2015

Cited by 6 | Viewed by 5831

Abstract

A 2 × 3 factorial study was conducted to evaluate the effects of dietary lipid level on the expression of mitochondrial and nuclear genes involved in electron transport chain in all-female rainbow trout Oncorhynchus mykiss. Three practical diets with a fixed crude protein content of 40%, formulated to contain 10% (40/10), 20% (40/20) and 30% (40/30) dietary lipid, were fed to apparent satiety to triplicate groups of either low-feed efficient (F120; 217.66 ± 2.24 g initial average mass) or high-feed efficient (F136; 205.47 ± 1.27 g) full-sib families of fish, twice per day, for 90 days. At the end of the experiment, the results showed that there is an interactive effect of the dietary lipid levels and the phenotypic feed efficiency (growth rate and feed efficiency) on the expression of the mitochondrial genes nd1 (NADH dehydrogenase subunit 1), cytb (Cytochrome b), cox1 (Cytochrome c oxidase subunits 1), cox2 (Cytochrome c oxidase subunits 2) and atp6 (ATP synthase subunit 6) and nuclear genes ucp2α (uncoupling proteins 2 alpha), ucp2β (uncoupling proteins 2 beta), pparα (peroxisome proliferator-activated receptor alpha), pparβ (peroxisome proliferatoractivated receptor beta) and ppargc1α (proliferator-activated receptor gamma coactivator 1 alpha) in fish liver, intestine and muscle, except on ppargc1α in the muscle which was affected by the diet and the family separately. Also, the results revealed that the expression of mitochondrial genes is associated with that of nuclear genes involved in electron transport chain in fish liver, intestine and muscle. Furthermore, this work showed that the expression of mitochondrial genes parallels with the expression of genes encoding uncoupling proteins (UCP) in the liver and the intestine of rainbow trout. This study for the first time presents the molecular basis of the effects of dietary lipid level on mitochondrial and nuclear genes involved in mitochondrial electron transport chain in fish. Full article

(This article belongs to the Special Issue Gene-Nutrient Interactions)

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Open AccessArticle

Gender Differences in the VDR-FokI Polymorphism and Conventional Non-Genetic Risk Factors in Association with Lumbar Spine Pathologies in an Italian Case-Control Study

by Alessandra Colombini, Marco Brayda-Bruno, Lucia Ferino, Giovanni Lombardi, Vincenzo Maione, Giuseppe Banfi and Sabina Cauci

Int. J. Mol. Sci. 2015, 16(2), 3722-3739; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms16023722 - 09 Feb 2015

Cited by 31 | Viewed by 5696

Abstract

Recently, the FokI polymorphism (rs2228570) in the vitamin D receptor gene (VDR) and conventional risk factors were associated with spine disorders in the Italian population, but without gender analysis. Two-hundred and sixty-seven patients (149 males, 118 females) with lumbar spine disorders were assessed by magnetic resonance imaging (MRI) and 254 (127 males, 127 females) asymptomatic controls were enrolled. The exposure to putative risk factors was evaluated and FokI polymorphism was detected by PCR-restriction fragment length polymorphism (PCR-RFLP). An association between lumbar spine pathologies and higher than average age; overweight; family history; lower leisure physical activity; smoking habit; higher number of hours/day exposure to vibration and more sedentary or intense physical job demand was observed in male patients. In contrast, in females, only higher age, overweight, family history and lower leisure physical activity were risk factors. FF genotype was a 2-fold risk factor to develop discopathies and/or osteochondrosis concomitant with disc herniation for both gender patients, while heterozygous Ff was protective for females only. In males only ff genotype was protective for discopathies and/or osteochondrosis and F allele was a 2-fold risk factor for hernia; discopathies; discopathies and/or osteochondrosis. Sex-related differences in voluntary behaviors, exposure to environmental risks and genetic background could be crucial for a gender-differentiated management of patients with spine disorders. Full article

(This article belongs to the Special Issue Gene-Nutrient Interactions)

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Open AccessArticle

No Association between HMOX1 and Risk of Colorectal Cancer and No Interaction with Diet and Lifestyle Factors in a Prospective Danish Case-Cohort Study

by Vibeke Andersen, Tine Iskov Kopp, Anne Tjønneland and Ulla Vogel

Int. J. Mol. Sci. 2015, 16(1), 1375-1384; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms16011375 - 07 Jan 2015

Cited by 6 | Viewed by 5931

Abstract

Red meat is a risk factor for colorectal cancer (CRC). We wanted to evaluate whether a functional polymorphism in the HMOX1 gene encoding heme oxygenase modifies risk of CRC or interacts with diet or lifestyle factors because this would identify heme or heme iron as a risk factor of CRC. The HMOX1 A-413T (rs2071746) was assessed in relation to risk of colorectal cancer (CRC) and interactions with diet (red meat, fish, fiber, cereals, fruit and vegetables) and lifestyle (use of non-steroidal anti-inflammatory drug and smoking status) were assessed in a case-cohort study of 928 CRC cases and a comparison group of 1726 randomly selected participants from a prospective study of 57,053 persons. No association between HMOX1 A-413T and CRC risk was found (TT vs. AA + TA; IRR = 1.15, 95% CI: 0.98–1.36, p = 0.10 for the adjusted estimate). No interactions were found between diet or lifestyle and HMOX1 A-413T. HMOX1 A-413T was not associated with CRC risk and no interactions with diet or lifestyle were identified in this large, prospective cohort with high meat intake. The results reproduced the previous findings from the same cohort and did not support a link between heme or heme iron and colorectal cancer. These results should be sought and replicated in other well-characterized cohorts with high meat intake. Full article

(This article belongs to the Special Issue Gene-Nutrient Interactions)

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Open AccessArticle

Long-Term Effects of Maternal Citrulline Supplementation on Renal Transcriptome Prevention of Nitric Oxide Depletion-Related Programmed Hypertension: The Impact of Gene-Nutrient Interactions

by You-Lin Tain, Chien-Te Lee and Li-Tung Huang

Int. J. Mol. Sci. 2014, 15(12), 23255-23268; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms151223255 - 15 Dec 2014

Cited by 17 | Viewed by 5903

Abstract

Maternal malnutrition can elicit gene expression leading to fetal programming. l-citrulline (CIT) can be converted to l-arginine to generate nitric oxide (NO). We examined whether maternal CIT supplementation can prevent N^G-nitro-l-arginine-methyl ester (l-NAME, NO synthase inhibitor)-induced programmed hypertension and examined their effects on the renal transcriptome in male offspring using next generation RNA sequencing (RNA-Seq) technology. Pregnant Sprague-Dawley rats received l-NAME administration at 60mg/kg/day subcutaneously via osmotic minipump during pregnancy alone or with additional 0.25% l-citrulline solution in drinking water during the whole period of pregnancy and lactation. Male offspring were assigned to three groups: control, l-NAME, and l-NAME + CIT. l-NAME exposure induced hypertension in the 12-week-old offspring, which CIT therapy prevented. Identified differentially expressed genes in l-NAME and CIT-treated offspring kidneys, including Guca2b, Hmox1, Hba2, Hba-a2, Dusp1, and Serpine1 are related to regulation of blood pressure (BP) and oxidative stress. In conclusion, our data suggests that the beneficial effects of CIT supplementation are attributed to alterations in expression levels of genes related to BP control and oxidative stress. Our results suggest that early nutritional intervention by CIT has long-term impact on the renal transcriptome to prevent NO depletion-related programmed hypertension. However, our RNA-Seq results might be a secondary phenomenon. The implications of epigenetic regulation at an early stage of programming deserve further clarification. Full article

(This article belongs to the Special Issue Gene-Nutrient Interactions)

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Review

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Open AccessReview

Neurological and Epigenetic Implications of Nutritional Deficiencies on Psychopathology: Conceptualization and Review of Evidence

by Jianghong Liu, Sophie R. Zhao and Teresa Reyes

Int. J. Mol. Sci. 2015, 16(8), 18129-18148; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms160818129 - 05 Aug 2015

Cited by 13 | Viewed by 9382

Abstract

In recent years, a role for epigenetic modifications in the pathophysiology of disease has received significant attention. Many studies are now beginning to explore the gene–environment interactions, which may mediate early-life exposure to risk factors, such as nutritional deficiencies and later development of behavioral problems in children and adults. In this paper, we review the current literature on the role of epigenetics in the development of psychopathology, with a specific focus on the potential for epigenetic modifications to link nutrition and brain development. We propose a conceptual framework whereby epigenetic modifications (e.g., DNA methylation) mediate the link between micro- and macro-nutrient deficiency early in life and brain dysfunction (e.g., structural aberration, neurotransmitter perturbation), which has been linked to development of behavior problems later on in life. Full article

(This article belongs to the Special Issue Gene-Nutrient Interactions)

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Milk—A Nutrient System of Mammalian Evolution Promoting mTORC1-Dependent Translation

by Bodo C. Melnik

Int. J. Mol. Sci. 2015, 16(8), 17048-17087; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms160817048 - 27 Jul 2015

Cited by 84 | Viewed by 24726

Abstract

Based on own translational research of the biochemical and hormonal effects of cow’s milk consumption in humans, this review presents milk as a signaling system of mammalian evolution that activates the nutrient-sensitive kinase mechanistic target of rapamycin complex 1 (mTORC1), the pivotal regulator of translation. Milk, a mammary gland-derived secretory product, is required for species-specific gene-nutrient interactions that promote appropriate growth and development of the newborn mammal. This signaling system is highly conserved and tightly controlled by the lactation genome. Milk is sufficient to activate mTORC1, the crucial regulator of protein, lipid, and nucleotide synthesis orchestrating anabolism, cell growth and proliferation. To fulfill its mTORC1-activating function, milk delivers four key metabolic messengers: (1) essential branched-chain amino acids (BCAAs); (2) glutamine; (3) palmitic acid; and (4) bioactive exosomal microRNAs, which in a synergistical fashion promote mTORC1-dependent translation. In all mammals except Neolithic humans, postnatal activation of mTORC1 by milk intake is restricted to the postnatal lactation period. It is of critical concern that persistent hyperactivation of mTORC1 is associated with aging and the development of age-related disorders such as obesity, type 2 diabetes mellitus, cancer, and neurodegenerative diseases. Persistent mTORC1 activation promotes endoplasmic reticulum (ER) stress and drives an aimless quasi-program, which promotes aging and age-related diseases. Full article

(This article belongs to the Special Issue Gene-Nutrient Interactions)

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Transcriptional Factors Mediating Retinoic Acid Signals in the Control of Energy Metabolism

by Rui Zhang, Yueqiao Wang, Rui Li and Guoxun Chen

Int. J. Mol. Sci. 2015, 16(6), 14210-14244; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms160614210 - 23 Jun 2015

Cited by 59 | Viewed by 10604

Abstract

Retinoic acid (RA), an active metabolite of vitamin A (VA), is important for many physiological processes including energy metabolism. This is mainly achieved through RA-regulated gene expression in metabolically active cells. RA regulates gene expression mainly through the activation of two subfamilies in the nuclear receptor superfamily, retinoic acid receptors (RARs) and retinoid X receptors (RXRs). RAR/RXR heterodimers or RXR/RXR homodimers bind to RA response element in the promoters of RA target genes and regulate their expressions upon ligand binding. The development of metabolic diseases such as obesity and type 2 diabetes is often associated with profound changes in the expressions of genes involved in glucose and lipid metabolism in metabolically active cells. RA regulates some of these gene expressions. Recently, in vivo and in vitro studies have demonstrated that status and metabolism of VA regulate macronutrient metabolism. Some studies have shown that, in addition to RARs and RXRs, hepatocyte nuclear factor 4α, chicken ovalbumin upstream promoter-transcription factor II, and peroxisome proliferator activated receptor β/δ may function as transcriptional factors mediating RA response. Herein, we summarize current progresses regarding the VA metabolism and the role of nuclear receptors in mediating RA signals, with an emphasis on their implication in energy metabolism. Full article

(This article belongs to the Special Issue Gene-Nutrient Interactions)

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