Journal of Nutrigenetics and Nutrigenomics最新文献

Background/aims: Nutrigenomics New Zealand has invested considerable effort researching the role of nutrient-gene interactions in human inflammatory bowel disease (IBD). This research has utilised a number of 'omics' techniques, including proteomics and metabolomics.

Methods: Mouse models of intestinal inflammation have been used to investigate the mechanisms underlying IBD and to test foods or food components for potential beneficial effects. Proteomics combining two-dimensional gel electrophoresis with liquid chromatography-mass spectrometry (LC-MS) analysis of peptides, and metabolomics using both gas chromatography-MS and LC-MS have been combined with transcriptomics and microbiome analyses to comprehensively assess samples derived from these models.

Results: Across several independent studies, we have identified key proteins and metabolites which are involved in chronic inflammation. We have also identified food compounds such as polyphenols (green tea polyphenols or curcumin) and polyunsaturated fatty acids, or whole foods such as salmon and broccoli, that reduce inflammation by regulating the activity of these proteins and metabolites.

Conclusions: Omics techniques, including proteomics and metabolomics, have deepened our insight into the mechanisms underlying intestinal inflammation, and how nutrient-gene interactions may influence these. However, challenges remain in dealing with the enormous quantity of data generated by these techniques, and in utilising these data to improve the outcome for people with IBD.

Background and aims: Circulating microRNAs (miRNAs) are linked to disease and are potential biomarkers. Vitamin D may modulate miRNA profiles, and vitamin D status has been linked to risk of disease, including cardiovascular disease and cancers. We hypothesise that genotypic variance influences these relationships. We examined the correlations between vitamin D intake and circulating levels of the miRNAs let-7a/b, and the involvement of two common vitamin D receptor (VDR) polymorphisms, BsmI and ApaI.

Methods: Two hundred participants completed food frequency and supplement questionnaires, and were assayed for circulating let-7b expression by qPCR. Polymorphisms were detected using restriction fragment length polymorphism-PCR.

Results: let-7b expression negatively correlated with vitamin D intake (rs=-0.20, p=0.005). The magnitude and direction of correlation were maintained in the presence of the BsmI restriction site (rs=-0.27, p=0.0005). However, in the absence of BsmI restriction site, the direction of the correlation was reversed (rs=+0.319, p=0.0497). These correlations were significantly different (z-score=2.64, p=0.0085). The correlation between vitamin D intake and let-7a was only significant in those without the ApaI restriction site.

Conclusions: The correlation between vitamin D intake and let-7a/b expression in this cohort varies with VDR genotype. This study highlights the importance of considering underlying genotypic variance in miRNA expression studies and in nutritional epigenetics generally.

Background/aims: Investigation of the genetic makeup may facilitate the implementation of more personalized nutritional interventions. The aims were to examine whether the rs10830963 MTNR1B polymorphism affects weight loss in response to a hypocaloric diet and to find potential gene-gene interplays and gene-diet interactions.

Methods: 167 subjects enrolled in a personalized nutritional intervention for weight loss (3-6 weeks) were examined for anthropometric measurements, dietary habits and physical activity at baseline and at the first follow-up visit. Three polymorphisms, which have previously been associated with body weight regulation, rs10830963 (MTNR1B), rs9939609 (FTO) and rs17782313 (MC4R), were analyzed using the Luminex® 100/200™ System.

Results: After adjusting for covariates, females with the rs10830963 CG/GG genotype showed lower weight loss than those with the CC genotype. In the total population, carriers of variant alleles of both FTO and MC4R showed a significant association with MTNR1B and weight loss outcome. Moreover, among women, higher total protein and animal protein intakes were associated with a lower weight loss in G allele carriers of the MTNR1B variant.

Conclusions: Our data evidenced that rs10830963 MTNR1B polymorphism could be associated with individual differences in weight loss induced by a hypocaloric diet. This association was influenced by FTO and MC4R loci and modified by baseline protein intake.

Background/aims: Gene-dietary pattern interactions may contribute to the determination of a susceptibility to metabolic syndrome (MetS). The aim of this study was to evaluate the potential interactions of dietary patterns with the common genetic variant of APOC3 in relation to MetS in adults.

Methods: In this individual matched nested case-control study, 755 MetS subjects and 755 controls were selected from among participants in the Tehran Lipid and Glucose Study. Dietary patterns were determined by factor analysis. APOC3 3238C>G rs5128 was genotyped by polymerase chain reaction and restriction fragment length polymorphism.

Results: Fat-sweet, healthy and Western dietary patterns (WDP) were extracted from the data. In the joint analysis, the associations of the WDP and APOC3 rs5128 with MetS risk tended to be dependent on APOC3 3238C>G gene variants (p for interaction = 0.009) in women. The MetS risk was increased in women with the CC genotype with increasing tertiles of WDP scores compared with women with the CG + GG genotype, whose MetS risk was decreased with increasing tertiles of WDP scores. In addition, we found that intakes of fast food, salty snacks and soft drinks showed significant interactions with the rs5128 genotypes in relation to MetS risk (p for interactions <0.05).

Conclusion: The results obtained demonstrate a diet-gene interaction between APOC3 rs5128 polymorphism and the WDP in relation to MetS risk.

Aims: The present study aimed to investigate the interaction between erythrocyte phospholipid (PL) fatty acids and variants of inflammation-related genes in a Chinese population.

Methods: A total of 622 patients with type 2 diabetes mellitus (T2DM) and 293 healthy subjects were included. Determination of erythrocyte PL fatty acids composition and genotyping of single nucleotide polymorphisms were conducted by standard methods.

Results: A significant interaction of rs7305618 on HNFIA with C18:2n-6 and C20:4n-6 was observed: T allele carriers (TT+CT) had a higher risk of T2DM than noncarriers only when they had a higher level of C18:2n-6 or C20:4n-6, and the odds ratios (ORs) were 2.59 (95% CI 1.58-4.24; p for interaction=0.005) and 2.49 (95% CI 1.47-4.24; p for interaction=0.021), respectively. A significant interaction of rs8078723 at the intergenic region between PSMD3 and CSF3 with C20:5n-3 was observed: C allele carriers (CC+CT) had a lower risk of T2DM than noncarriers only when they had a higher level of C20:5n-3, and the OR was 0.44 (95% CI 0.26-0.73; p for interaction=0.014).

Conclusions: rs7305618 and rs8078723 were associated with the risk of T2DM in a Chinese population and were modulated by erythrocyte PL fatty acids composition.

Of all chronic metabolic diseases, cardiovascular disease (CVD) is the leading cause of death worldwide. Most research over the past 100 years show a link between CVD and lifestyle, including diet; thus, public health messages have focused on modifications of the diet to better manage this disease. Despite this effort, the CVD mortality rate continues to rise. Therefore, is it possible that this failure may be due to individual variability in response to dietary recommendations? The elucidation of the structure of the human genome combined with the knowledge that nutrients are capable of modifying gene expression and genetic variability regulates how individuals respond to a diet have led to the possibility of personalized nutrition for disease prevention. While this possibility is real for the future, our current understanding of nutrient-gene interactions for CVD is limited, making personalized nutrition therapy difficult at this time. With advances in nutritional genomics, in the near future, dietitians and nutritionists will be able to give personalized nutritional advice based on a combination of lifestyle factors and genetics.

Background: Targeting telomerase is a potential cancer management strategy given that it allows unlimited cellular replication in the majority of cancers. Dysfunctional telomeres are recognized as double-strand breaks. However, the status of DNA repair response pathways following telomerase inhibition is not well understood in human breast cancer cells. Here, we evaluated the effects of MST-312, a chemically modified derivative from tea catechin, epigallocatechin gallate, on telomere dynamics and DNA damage gene expression in breast cancer cells.

Methodology: Breast cancer cells MCF-7 and MDA-MB-231 were treated with MST-312, and telomere-telomerase homeostasis, induced DNA damage and gene expression profiling were analyzed.

Results: MST-312 decreased telomerase activity and induced telomere dysfunction and growth arrest in breast cancer cells with more profound effects in MDA-MB-231 than in MCF-7 cells. Consistent with these data, the telomere-protective protein TRF2 was downregulated in MDA-MB-231 cells. MST-312 induced DNA damage at telomeres accompanied by reduced expression of DNA damage-related genes ATM and RAD50. Co-treatment with MST-312 and the poly(ADP-ribose) polymerase 1 (PARP-1) inhibitor PJ-34 further enhanced growth reduction as compared to single treatment with MST-312 or PJ-34.

Conclusions: Our work demonstrates potential importance for the establishment of antitelomerase cancer therapy using MST-312 along with PARP-1 inhibition in breast cancer therapy.

Background/aims: To examine whether a family history of dyslipidemia influences the lipid-lipoprotein response to the Mediterranean diet (MedDiet).

Methods: We recruited 36 individuals with a positive family history of dyslipidemia (i.e. having at least one first-degree relative with a diagnosis of dyslipidemia) and 28 individuals with a negative family history of dyslipidemia, aged between 24 and 53 years, who had slightly elevated low-density lipoprotein cholesterol (LDL-C) concentrations (3.4-4.9 mmol/l) or a total cholesterol to high-density lipoprotein cholesterol (HDL-C) ratio≥5.0. Variables related to the lipid-lipoprotein profile were measured before and after a 4-week isocaloric MedDiet during which all foods and drinks were provided to participants.

Results: A group by time interaction was noted for plasma total cholesterol concentrations (p=0.03), subjects with a negative family history of dyslipidemia having greater decreases than those with a positive family history of dyslipidemia (-11.3 vs. -5.1%, respectively). Decreases in LDL-C, HDL-C, total cholesterol to HDL-C ratio, LDL-C to HDL-C ratio, apo B, apo A-1, apo A-2 and apo B to apo A-1 ratio were noted, with no difference between groups (p for group by time interaction≥0.11).

Conclusions: Results highlight that inherited susceptibilities to dyslipidemia may explain at least in part the heterogeneity in the cholesterol-lowering effects of the MedDiet.

Background/aim: We studied the molecular pathogenesis of obesity, involving complex interactions between environmental and genetic factors, with a focus on the leptin gene. It was our aim to characterize the LEP -2548G>A leptin polymorphism and lipid profile in obese and normal-weight individuals.

Methods: A total of 212 individuals were divided into the study group including 136 obese patients (body mass index, BMI≥30) and the control group with 76 normal-weight individuals (BMI>18.5 and ≤24.9). DNA was amplified by polymerase chain reaction and restriction fragment length polymorphism. The lipid profile was analyzed by enzymatic colorimetric methods. The level of significance was set at p<0.05.

Results: There was a prevalence of the GA genotype in both groups. However, comparative group analysis showed an association of the recessive model (AA+GA) with increased triglycerides (TG) and decreased high-density lipoprotein cholesterol (HDL-C) levels in the study group.

Conclusion: This study did not confirm an association between obesity and the LEP -2548G>A polymorphism. However, AA+GA genotypes, in the presence of obesity, seem to contribute to a reduction in HDL-C and an increase in TG compared with normal-weight individuals. This should be confirmed in further studies.