Journal of Nutrigenetics and Nutrigenomics最新文献

Background: Recently, we have shown anti-proliferative and pro-apoptotic effects of indicaxanthin associated with epigenetic modulation of the onco-suppressor p16INK4a in the human colon cancer cell line CACO2. In the present study, the epigenetic activity of indicaxanthin and the mechanisms involved were further investigated in other colorectal cancer cell lines.

Methods: LOVO1, CACO2, HT29, HCT116, and DLD1 cells were used to evaluate the potential influence of consistent dietary concentrations of indicaxanthin on DNA methylation, and the epigenetic mechanisms involved were researched.

Results: Indicaxanthin exhibited anti-proliferative activity in all cell lines but HT29, induced demethylation in the promoters of some methylation-silenced onco-suppressor genes involved in colorectal carcinogenesis (p16INK4a, GATA4, and ESR1), and left unchanged others which were basally hypermethylated (SFRP1 and HPP1). In apparent contrast, cell exposure to indicaxanthin increased DNMT gene expression, although indicaxanthin appeared to be an inhibitor of DNMT activity. Indicaxanthin also increased the expression of genes involved in DNA demethylation. Finally, an in silico molecular modelling approach suggested stable binding of indicaxanthin at the DNMT1 catalytic site.

Conclusions: Our findings contribute to new knowledge in the field of phytochemicals and specifically suggest dietary indicaxanthin as a potential epigenetic agent to protect colon cells against tumoral alterations.

Red meat may increase promutagenic lesions in the colon. Resistant starch (RS) can reduce these lesions and chemically induced colon tumours in rodents. Msh2 is a mismatch repair (MMR) protein, recognising unrepaired promutagenic adducts for removal. We determined if red meat and/or RS modulated DNA adducts or oncogenesis in Msh2-deficient mice. A total of 100 Msh2-/- and 60 wild-type mice consumed 1 of 4 diets for 6 months: control, RS, red meat and red meat+RS. Survival time, aberrant crypt foci (ACF), colon and small intestinal tumours, lymphoma, colonic O6-methyl-2-deoxyguanosine (O6MeG) adducts, methylguanine methyltransferase (MGMT) and cell proliferation were examined. In Msh2-/- mice, red meat enhanced survival compared to control (p<0.01) and lowered total tumour burden compared to RS (p<0.167). Msh2-/- mice had more ACF than wild-type mice (p<0.014), but no colon tumours developed. Msh2-/- increased cell proliferation (p<0.001), lowered DNA O6MeG adducts (p<0.143) and enhanced MGMT protein levels (p<0.001) compared to wild-type mice, with RS supplementation also protecting against DNA adducts (p<0.01). No link between red meat-induced promutagenic adducts and risk for colorectal cancer was observed after 6 months' feeding. Colonic epithelial changes after red meat and RS consumption with MMR deficiency will differ from normal epithelial cells.

Background/aims: The influence of TAS2R38 haplotype on the relationship between the perceived intensity of propylthiouracil (PROP) and the basic tastes of salt, sweet, sour, and bitter (quinine) was evaluated in the Beaver Dam Offspring Study.

Methods: Genotyping was performed on 1,670 participants aged ≥45 years (mean age = 54.4; range = 45-84), and suprathreshold taste intensity was measured using filter paper disks and a general labeled magnitude scale (0-100).

Results: Among those with taste intensity data and the PAV or AVI haplotype (n = 1,258), the mean perceived intensity of PROP was 37.3 (SD = 30.0), but it varied significantly (p < 0.0001) by diplotype (PAV/PAV = 60.1; PAV/AVI = 46.5; AVI/AVI = 14.4). PROP intensity was correlated with the basic taste intensities (salt: r = 0.22; sweet: r = 0.25; sour: r = 0.21; quinine bitterness: r = 0.38; p < 0.001 for all tastes); however, a significant effect modification of the PROP-taste intensity relationships by TAS2R38 diplotype was observed. There was a stronger association between PROP and each of the basic tastes in the PAV/PAV diplotype group than in the other groups.

Conclusions: Directly measuring the perceived intensity of the 4 tastes, rather than using PROP intensity as an indicator of taste responsiveness, is recommended for studies of taste perception.

Aim: To assess the behavioral effects of receiving personal genetic information, using apoE genotypes as a tool for promoting lifestyle changes. apoE was chosen because it has a significant impact on lipid metabolism and cholesterol absorption, both factors in cardiovascular disease.

Methods: This study was a 1-year intervention study of healthy adults aged 20-67 years (n = 107). Their behavioral changes were measured by diet (e.g., fat quality, as well as consumption of vegetables, berries, fruits, and fatty and sugary foods), alcohol consumption, and exercise. Health and taste attitudes were assessed with the Health and Taste Attitude Scales (HTAS). The measurements were performed 4 times: at baseline (T0), as well as 10 weeks (T1), 6 months (T2), and 12 months after baseline (T3). These behavioral effects were assessed for three groups: a high-risk (Ɛ4+; n = 16), a low-risk (Ɛ4-; n = 35), and a control group (n = 56).

Results: Personal genetic information affected health behavior. Dietary fat quality improved more in the Ɛ4+ group than in the Ɛ4- and control groups after personal, genotype-based health advice. This change differed significantly between the Ɛ4+ and the control group (p < 0.05), but only for a short time.

Conclusion: Personal genetic information, based on apoE, may affect dietary fat quality. More research is required to determine how to utilize genotype-based health information and how to efficiently achieve long-term changes in the prevention of lifestyle-related diseases.

Background/aim: Genetic variation in apolipoprotein E (ApoE) has a key role in lipid metabolism. However, its contribution to the amount and distribution of body fat is under investigation. The aim of this study was to analyze the association between genetic variation in ApoE and obesity-related traits in Mexican school children.

Material and methods: Anthropometric, body composition and physical activity measures were conducted using standard methods in 300 children (177 girls/123 boys) who fulfilled the inclusion criteria. DNA was isolated from saliva. ApoE genotypes were analyzed by allelic discrimination. The association between variation in ApoE and anthropometric and body composition measures was investigated using the General Linear Model.

Results: The mean±SD values for age, body mass index (BMI) and waist circumference (WC) were 9.05±0.80 years, 19.01±3.83 and 67.98±10.97 cm, respectively. Approximately 46% of the participants were overweight or obese. A significant association between ApoE isoforms and WC was found after controlling for age, sex and the percentage of physical activity (p=0.025). Significant main effects were found for vigorous physical activity and light physical activity influencing the adiposity-related BMI (p<0.001) and WC (p=0.044), respectively.

Conclusions: Variation in ApoE and physical activity intensity were associated with adiposity-related phenotypes in Mexican school children.

Background/aims: Direct-to-consumer (DTC) genetic tests have facilitated easy access to personal genetic information related to health and nutrition; however, consumer perceptions of the nutritional information provided by these tests have not been evaluated. The objectives of this study were to assess individual perceptions of personalized nutrition and genetic testing and to determine whether a personalized nutrition intervention modifies perceptions.

Methods: A double-blind, parallel-group, randomized controlled trial was conducted among healthy men and women aged 20-35 years (n = 138). Participants in the intervention group (n = 92) were given a report of DNA-based dietary advice and those in the control group (n = 46) were given a general dietary advice report. A survey was completed at baseline and 3 and 12 months after distributing the reports to assess perceptions between the two groups.

Results: No significant differences in perceptions of personalized nutrition and genetic testing were observed between the intervention and control group, so responses of both groups were combined. As compared to baseline, participant responses increased significantly toward the positive end of a Likert scale at 3 months for the statement 'I am interested in the relationship between diet and genetics' (mean change ± SD: 0.28 ± 0.99, p = 0.0002). The majority of participants indicated that a university research lab (47%) or health care professional (41%) were the best sources for obtaining accurate personal genetic information, while a DTC genetic testing company received the fewest selections (12%). Most participants (56%) considered dietitians to be the best source of personalized nutrition followed by medical doctors (27%), naturopaths (8%) and nurses (6%).

Conclusions: These results suggest that perceptions of personalized nutrition changed over the course of the intervention. Individuals view a research lab or health care professional as better providers of genetic information than a DTC genetic testing company, and registered dietitians are considered to be the best providers of personalized nutrition advice.

Background: Fibroblast growth factor 21 (FGF21) is a hormone involved in the metabolism of carbohydrates and lipids. Increased circulating FGF21 levels are closely associated with nonalcoholic fatty liver disease (NAFLD). However, the association between genetic variations of FGF21 and NAFLD remains unknown. In our study, we aimed to investigate the association of these genetic variations with serum FGF21 levels and NAFLD.

Methods: We genotyped four single nucleotide polymorphisms (SNPs) in FGF21 and its flanking region in 340 nondiabetic subjects. NAFLD was defined as the presence of a specific abdominal ultrasonographic pattern. Serum FGF21 concentrations were measured using an enzyme-linked immunosorbent assay kit.

Results: We found significant evidence of an association with NAFLD for rs499765 (p = 0.039). After adjusting for age and sex, the effect of rs499765 on NAFLD remained significant (p = 0.045). However, after adjusting for multiple comparisons, no association was found. Moreover, rs499765 was associated with serum FGF21 levels (p = 0.030). In addition, both rs2071699 and rs838136 showed an association with serum aspartate aminotransferase levels (p = 0.049 and p = 0.047, respectively). The SNP rs838136 also showed a correlation with serum alanine aminotransferase concentrations after adjustment for body mass index (p = 0.034). We also combined the minor group with the heterozygous genotype and observed that rs499765 had an effect on FGF21 (p = 0.031).

Conclusion: The variant rs499765 adjacent to FGF21 is associated with serum FGF21 levels and NAFLD in a Chinese nondiabetic population.

Background/aims: The objective of this preliminary study was to examine the impact of the Mediterranean diet (MedDiet) on the high-density lipoprotein (HDL) proteome in men with the metabolic syndrome (MetS).

Methods: Twenty-six men with the MetS first consumed a standardized baseline North American isoenergetic control diet (5 weeks) and then consumed an isoenergetic MedDiet (5 weeks), both in full feeding condition. The HDL fraction was isolated by ultracentrifugation at the end of each diet and the HDL proteome assessed by isobaric tags for relative and absolute quantitation and mass spectrometry.

Results: Of all proteins identified within HDL, only 3 showed significant changes in relative abundance after the MedDiet versus the control diet, including a reduction in inflammation-related inter-α-trypsin inhibitor heavy chain H4 (fold change: 0.62) and hemoglobin subunits α (fold change: 0.40) and β (fold change: 0.46). Other HDL-bound proteins associated with functions related to lipid metabolism/cholesterol homeostasis, oxidation, coagulation, complement activation and immunity were unchanged after consumption of the MedDiet for 5 weeks.

Conclusions: Changes in the HDL proteome may explain, at least partly, the well-known anti-inflammatory effect ascribed to the MedDiet. Otherwise, short-term consumption of the MedDiet seems to have little impact on other features of the HDL proteome in men with the MetS.

Background/aims: An association of genetic variants of homocysteine (Hcy) metabolic genes with type 2 diabetes mellitus (T2DM) has been reported. The objective of the present study was to investigate the relationship between the genetic variants in Hcy metabolism-related genes and plasma Hcy levels and T2DM susceptibility in Han Chinese.

Methods: A total of 774 patients with T2DM and 500 healthy individuals were recruited. Single-nucleotide polymorphism was determined by standard methods.

Results: The Hcy-increasing allele score was positively associated with plasma Hcy levels in both T2DM patients and healthy subjects (r = 0.171 and 0.247, respectively). Subjects with the genotype CC of MTHFR (rs1801131) had a significantly higher likelihood of T2DM compared with subjects with the AA or AA+AC genotypes (OR = 1.93 for CC vs. AA, p = 0.041; OR = 3.13 for CC vs. AA+AC, p = 0.017, respectively). Subjects with the genotype AA of the MTHFD variant (rs2236225) had a significantly lower likelihood of T2DM compared with subjects with the GG or GG+GA genotypes (OR = 0.36 for AA vs. GG, p = 0.027; OR = 0.36 for AA vs. GG+GA, p = 0.017, respectively). In addition, the genotype CT+TT of the PEMT (rs4646356) variants displayed a significant association with an increased risk of T2DM (OR = 1.52 for CT+TT vs. CC, p = 0.042).

Conclusions: MTHFR rs1801131 C allele and PEMT rs4646356 T allele were associated with a high risk of T2DM in these Han Chinese.

Background/aims: Single nucleotide polymorphisms (SNPs) in the ADIPOQ gene could explain the adiponectin level. However, the knowledge about the influence of genetic and lifestyle factors is not sufficient. The aim was to analyze whether the effect of the -11391G/A SNP in the ADIPOQ gene is modulated by lifestyle factors in Mexican subjects.

Methods: A cross-sectional study was performed in which 394 participants were analyzed. Genetic, anthropometric, biochemical, dietary, clinical and physical activity parameters were measured. Statistical analysis was performed with SPSSv19 software.

Results: The distribution of the -11391G/A SNP genotypes was 55.6 and 44.4% for GG and AG, respectively. The adiponectin level was modulated by the -11391G/A SNP in response to the body mass index (BMI); A allele carriers showed a higher adiponectin level compared to G homozygous carriers but only in the minor BMI tertile group (p=0.032). Adiponectin level variability was explained by gender [(r)=1.5, 95% CI 1.1-1.9, p=0.000], insulin resistance [(r)=-1.2, 95% CI -0.8 to -1.6, p=0.000], physical activity [(r)=0.6, 95% CI 0.2-0.9, p=0.002] and monounsaturated fat intake [(r)=0.5, 95% CI 0.38-1.0, p=0.047].

Conclusions: The adiponectin level was modulated by the interaction between BMI and -11391G/A SNP; this suggests that the lifestyle rather than genetic factors modulates serum adiponectin.