Journal of Nutrigenetics and Nutrigenomics最新文献

Background: Diet is known to play a major role in Crohn's disease (CD). It has also been reported that the minor G allele from the rs12212067 polymorphism (T>G) in FOXO3 is associated with milder CD. The aim of this study was to investigate the association between the rs12212067 polymorphism and food intolerances for a total of 253 foods.

Methods: Tolerances and intolerances were recorded on a self-reported dietary questionnaire. Each food was scored on a 5-point ordinal scale: beneficial effects as '+ +' or '+', adverse effects as '- -' or '-', and 'makes no difference' as '='. Dietary and genotype data were available for a total of 283 CD patients.

Results: We identified 17 foods with beneficial effects in our study which were significantly associated with the G allele of the FOXO3 rs12212067 polymorphism. Of these, sweet potatoes had the highest reported frequency of beneficial responses. We also identified 4 foods with detrimental effects in more than 25% of our study population. These were mustard, wasabi, and raw and cooked tomatoes, which again were significantly associated with the G allele in FOXO3.

Conclusions: There was strong evidence that adverse effects of mustard, wasabi, and raw and cooked tomatoes were significantly associated with the G allele of FOXO3 and that these foods should be avoided by people carrying this allele.

Background/aims: Diabetes mellitus type 2 (DMT2) is accompanied by systemic low-grade inflammation with elevated levels of interleukin-6 (IL-6), which is encoded by a gene (IL-6) previously shown to be regulated by DNA methylation. We investigated seven CpG sites in IL-6 in individuals with DMT2, obese individuals and lean controls. Further, the DMT2 group received the glucagon-like peptide 1 agonist liraglutide.

Methods: Blood samples were taken at the beginning of the study and after 4 months. The DNA methylation was assessed using pyrosequencing.

Results: Methylation levels at the CpG sites -664, -628 and +13 at the first sampling time point (T1) and at -666 and -664 at the second sampling time point (T2) correlated negatively with initial body weight in the DMT2 group. We found positive correlations for the obese and the lean control group. In the obese group, CpG +27 methylation at T1 correlated with initial body weight (r = 0.685; p = 0.014). In the lean group, CpG -664 at T1 (r = 0.874; p = 0.005) and CpG -628 at T2 (r = 0.632; p = 0.050) correlated with initial body weight.

Conclusion: These findings are an informative basis for further studies to elucidate epigenetic mechanisms underlying DMT2. Additionally, our results might provide starting points for the development of biomarkers for prevention and therapy strategies.

Background/aims: To determine whether variation in the TAS1R2 gene affects sucrose taste perception and sugar intake.

Methods: Participants were men (n = 238) and women (n = 458) aged 20-29 years. A subset (n = 95) with body mass index (BMI) data available completed a sensory analysis study. A food frequency questionnaire assessed dietary intake, and eight polymorphisms were genotyped (rs12033832, rs12137730, rs35874116, rs3935570, rs4920564, rs4920566, rs7513755 and rs9701796). Sucrose taste thresholds were determined by staircase procedure (solutions: 9 × 10-6 to 0.5 mol/l). Suprathreshold sensitivity to 0.01-1.0 mol/l sucrose solutions was assessed using general Labeled Magnitude Scales.

Results: A significant genotype-BMI interaction was observed for rs12033832 (G>A) for suprathreshold sensitivity (p = 0.01) and sugar intake (p = 0.003). Among participants with a BMI ≥25, G allele carriers had lower sensitivity ratings (mean incremental area under the taste sensitivity curve ± SE; GG/GA 54.4 ± 4.1 vs. AA 178.5 ± 66.6; p = 0.006), higher thresholds (GG/GA 9.3 ± 1.1 vs. AA 4.4 ± 4.3 mmol/l; p = 0.004) and consumed more sugars (GG/GA 130 ± 4 vs. AA 94 ± 13 g/day; p = 0.009). G allele carriers with a BMI <25 had lower thresholds (GG/GA 8.6 ± 0.5 vs. AA 16.7 ± 5.7 mmol/l; p = 0.02) and consumed less sugars (GG/GA 122 ± 2 vs. AA 145 ± 8 g/day; p = 0.004).

Conclusion: The rs12033832 single nucleotide polymorphism in TAS1R2 is associated with sucrose taste and sugar intake, but the effect differs depending on BMI.

Aim: The aim of this study was to investigate possible relationships among the A1298C (rs1801131) and C677T (rs1801133) polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and levels of homocysteine, vitamins B6, B12, folic acid and lipid profile, including oxidized low-density lipoprotein (ox-LDL), of adolescents at cardiovascular risk.

Methods: We recruited 115 adolescents (10-19 years old), 58.3% (n = 67) female, from a public school in Brazil who underwent anthropometric, biochemical and genetic tests as well as food consumption evaluation.

Results: An important prevalence of hyperhomocysteinemia (19.1%) and alterations in triacylglycerol (17.4%), total cholesterol (26.9%) and high-density lipoprotein (HDL) cholesterol (48.0%) concentrations were observed, as well as low vitamin B6 concentrations (23.5%). The categorization of homocysteine concentrations into tertiles revealed significant differences in serum concentrations of folate, vitamin B12 and HDL, waist circumference and intake of total and saturated fat among the tertiles. The presence of variant alleles regarding the MTHFR C677T polymorphism interfered with vitamin B6 and ox-LDL cholesterol concentrations. There was a trend for higher waist circumference values in T carriers (C677T), but not in C carriers (A1298C).

Conclusions: The MTHFR C677T allele was associated with higher plasma vitamin B6 and ox-LDL compared to the CC genotype.

Background/aims: Type 2 diabetes (T2D) is modulated by the interactions between genetic and dietary factors. This study sought to examine whether the associations of genome-wide association study (GWAS)-identified genetic variants with T2D risk were modulated by n-3 fatty acids in Chinese Hans.

Methods: Six hundred and twenty-two T2D patients and 293 healthy controls were recruited. Erythrocyte phospholipid fatty acids were measured by standard methods. Nine GWAS-identified T2D-related single-nucleotide polymorphisms (SNPs) were genotyped. These SNPs were all identified in GWAS of Asian populations with a high minor allele frequency (>0.2).

Results: Among the 9 SNPs, only rs3786897 at PEPD (peptidase D) showed a significant interaction with n-3 fatty acids (p(interaction) after Bonferroni correction = 0.027). The rs3786897 A allele was associated with a higher risk of T2D [GA+AA vs. GG: odds ratio (OR) = 2.16, 95% confidence interval (CI) 1.32-3.55] when n-3 fatty acids were lower than the population median, but no significant association (GA+AA vs. GG: OR = 0.63, 95% CI 0.35-1.12) was observed when n-3 fatty acids were higher than the median.

Conclusions: The association between the PEPD genetic variant and the risk of T2D was modulated by n-3 fatty acids. Higher n-3 fatty acids may abolish the adverse effect of the risk allele at PEPD for T2D.

Background/aim: Total fat intake has an important impact on the low-density lipoprotein (LDL) peak particle diameter (LDL-PPD) and may interact with nutrient-sensitive single nucleotide polymorphisms (SNPs). The objective was to examine whether there is suggestive evidence of SNP × dietary fat intake interaction effects influencing the LDL-PPD in the Quebec Family Study (QFS) in order to generate hypotheses to be tested in larger studies.

Methods: SNPs from a genome-wide association study (GWAS) using Illumina Human610-Quad BeadChip, total fat intake derived from a 3-day weighted food record, and SNP × total fat intake interaction effects were examined on LDL-PPD in 541 QFS subjects.

Results: The GWAS analyses 29 identified independent SNP × total fat intake interaction effects on the LDL-PPD at p < 10(-5), including SNPs in the following genes: ABCG2, CPA3, FNBP1, KCNQ3, NBAS, NCALD, OPRL1, NKAIN2, SH3BGRL2, SOX5, and SUSD4.

Conclusions: This observational study suggests that multiple SNPs interact with dietary fat intake to influence variation in the LDL-PPD.

Background: Observational research associating 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms with risk of autism, depression, cancer, and cardiovascular disease has led to increased diagnoses of MTHFR; however, doctors lack knowledge about safety, effectiveness, and clinical implications of MTHFR treatment. Treatment strategies are hypothetical and mechanistically based, including methylfolate with or without other B vitamins.

Aims: This study was designed to formally describe patient and health care provider experiences with the diagnosis and clinical management of MTHFR.

Methods: Guided by a structured interview guide, a qualitative study queried patients' and providers' observations regarding: testing indications, reaction to results, treatment protocols, and clinical response including adverse effects.

Results: Thirty patients and 8 doctors participated. Patient themes included emotionality associated with diagnosis, classification of signs and symptoms, and challenges with treatment. They expressed confusion over their diagnosis, and frustration with the state of knowledge their providers had regarding MTHFR. Testing indications included: fatigue (21%), hormone imbalances (13%), and neurological symptoms (13%) including brain fog (8%). Patients reported improvements in physical (60%) and mental/behavioral symptoms (36%) following treatment. A minority of participants reported side effects, but they occurred in almost every body system and ranged in severity. Doctors relied on trial and error to determine treatment doses, frequency and components.

Conclusions: MTHFR testing results in variable clinical processes in domains related to delivery of diagnosis and prognosis, and therapeutic options. However, patients report largely positive experiences. Clinicians and patients would benefit from therapeutic algorithms based on rigorous research.

Background and aims: The common polymorphism rs9939609 of the fat mass- and obesity-associated gene (FTO) has been linked to obesity. Our aim was to investigate its role in weight loss after the administration of a high-protein/low-carbohydrate diet compared to a standard hypocaloric diet (1,000 kcal/day).

Methods: During 9 months, 195 patients were randomly allocated to a high-protein hypocaloric diet (HP diet) and a standard hypocaloric diet (S diet).

Results: With the HP diet, BMI (-1.9 ± 1.2 vs. -2.10 ± 1.8; p < 0.05), weight (-6.5 ± 2.1 vs. -10.1 ± 4.1 kg; p < 0.05), fat mass (-3.9 ± 3.2 vs. -6.0 ± 3.4 kg; p < 0.05) and waist circumference (-5.7 ± 5.0 vs. -9.9 ± 5.5 cm; p < 0.05) decreased in both genotype groups (TT vs. AT + AA). With the S diet, BMI (-0.9 ± 1.1 vs. -1.8 ± 1.2; p < 0.05), weight (-3.2 ± 3.0 vs. -9.1 ± 3.6 kg; p < 0.05), fat mass (-3.0 ± 3.1 vs. -5.2 ± 3.1 kg; p < 0.05) and waist circumference (-3.1 ± 4.0 vs. -8.1 ± 4.9 cm; p < 0.05) decreased in both genotype groups. With the HP diet and in both genotype groups, glucose, insulin levels, homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol, triglycerides and low-density lipoprotein (LDL) decreased. With the S diet, total cholesterol and LDL decreased.

Conclusion: Weight loss was better in A allele carriers than noncarriers, and metabolic improvement was better with the HP diet.

Background/aims: Alzheimer's disease (AD) is an irreversible neurodegenerative disorder and is the commonest form of dementia. One aim of this study was to determine whether AD individuals have altered plasma folate, vitamin B12 and homocysteine (Hcy) levels compared to controls. The other aim was to investigate correlations between B vitamins and buccal biomarkers to test whether they are influenced by B vitamin status.

Methods: Folate, vitamin B12 and Hcy were measured using ARCHITECT® and AxSYM® assays. Genomic stability was measured using the buccal micronucleus cytome assay.

Results: The area under the receiver operating characteristic curve for AD basal cells was 0.96 (p < 0.0001), for karyorrhectic cells 0.88 (p < 0.0001) and for basal and karyorrhectic cells 0.91 (p < 0.0001). Hcy was significantly increased (p = 0.0003) compared to controls. Plasma vitamin B12 in controls showed a positive correlation with pyknosis (r = 0.5365, p = 0.004), karyolysis (r = 0.5447, p = 0.004) and condensed chromatin (r = 0.5238, p = 0.006). Plasma vitamin B12 in AD cases showed a positive correlation with micronuclei (r = 0.3552, p = 0.04) and basal cells (r = 0.3448, p = 0.04), whilst plasma Hcy showed a negative correlation with karyorrhectic cells (r = -0.4107, p = 0.01).

Conclusions: Hcy was significantly increased in AD cases relative to controls. The lower frequency of basal cells and karyorrhectic cells observed in AD cases may be explained by lower vitamin B12 and higher Hcy levels, respectively.

Background/aim: Sporadic breast cancer is frequently associated with aberrant DNA methylation patterns that are reversible and responsive to environmental factors, including diet. In the present study, we investigated the effects of sulforaphane (SFN), a phytochemical from cruciferous vegetables, on the methylation and expression of PTEN and RARbeta2 tumour suppressor genes as well as on the expression of regulators of DNA methylation reaction, DNMT1 , p53 , and p21 , in MCF-7 and MDA-MB-231 human breast cancer cells with different invasive potential. We also evaluate the role of SFN epigenetic effects in support of therapy with clofarabine (ClF) that was recently shown to modulate the epigenome as well.

Methods: Promoter methylation and gene expression were estimated using methylation-sensitive restriction analysis and real-time PCR, respectively.

Results: In both MCF-7 and MDA-MB-231 cells, SFN at IC 50 (22 and 46 μ M , respectively) and a physiologically relevant 10 μ M concentration lead to hypomethylation of PTEN and RARbeta2 promoters with concomitant gene upregulation. The combination of SFN and ClF enhances these effects, resulting in an increase in cell growth arrest and apoptosis at a non-invasive breast cancer stage.

Conclusions: Our findings provide evidence that SFN activates DNA methylation-silenced tumour suppressor genes in breast cancer cells and may contribute to SFN-mediated support of therapy with an anti-cancer drug, ClF, increasing its applications in solid tumours.