| 1. |
- Drake, Isabel, et al.
(författare)
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A prospective study of dietary and supplemental zinc intake and risk of type 2 diabetes depending on genetic variation in SLC30A8
- 2017
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Ingår i: Genes and Nutrition. - : Springer Science and Business Media LLC. - 1555-8932 .- 1865-3499. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: The solute carrier family 30 member 8 gene (SLC30A8) encodes a zinc transporter in the pancreatic beta cells and the major C-allele of a missense variant (rs13266634; C/T; R325W) in SLC30A8 is associated with an increased risk of type 2 diabetes (T2D). We hypothesized that the association between zinc intake and T2D may be modified by the SLC30A8 genotype. Results: We carried out a prospective study among subjects with no history cardio-metabolic diseases in the Malmö Diet and Cancer Study cohort (N = 26,132, 38% men; 86% with genotype data). Zinc intake was assessed using a diet questionnaire and food record. During a median follow-up of 19 years, 3676 T2D cases occurred. A BMI-stratified Cox proportional hazards regression model with attained age as the time scale was used to model the association between total and dietary zinc intake, zinc supplement use, zinc to iron ratio, and risk of T2D adjusting for putative confounding factors. The median total zinc intake was 11.4 mg/day, and the median dietary zinc intake was 10.7 mg/day. Zinc supplement users (17%) had a median total zinc intake of 22.4 mg/day. Dietary zinc intake was associated with increased risk of T2D (Ptrend < 0.0001). In contrast, we observed a lower risk of T2D among zinc supplement users (HR = 0.79, 95% CI 0.70–0.89). The SLC30A8 CC genotype was associated with a higher risk of T2D (HR = 1.16, 95% CI 1.07–1.24), and the effect was stronger among subjects with higher BMI (Pinteraction = 0.007). We observed no significant modification of the zinc-T2D associations by SLC30A8 genotype. However, a three-way interaction between SLC30A8 genotype, BMI, and zinc to iron ratio was observed (Pinteraction = 0.007). A high zinc to iron ratio conferred a protective associated effect on T2D risk among obese subjects, and the effect was significantly more pronounced among T-allele carriers. Conclusions: Zinc supplementation and a high zinc to iron intake ratio may lower the risk of T2D, but these associations could be modified by obesity and the SLC30A8 genotype. The findings implicate that when considering zinc supplementation for T2D prevention, both obesity status and SLC30A8 genotype may need to be accounted for.
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| 2. |
- Ericson, Ulrika, et al.
(författare)
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Dietary and genetic risk scores and incidence of type 2 diabetes
- 2018
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Ingår i: Genes and Nutrition. - : Springer Science and Business Media LLC. - 1555-8932 .- 1865-3499. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Both lifestyle and genetic predisposition determine the development of type 2 diabetes (T2D), and studies have indicated interactions between specific dietary components and individual genetic variants. However, it is unclear whether the importance of overall dietary habits, including T2D-related food intakes, differs depending on genetic predisposition to T2D. We examined interaction between a genetic risk score for T2D, constructed from 48 single nucleotide polymorphisms identified in genome-wide association studies, and a diet risk score of four foods consistently associated with T2D in epidemiological studies (processed meat, sugar-sweetened beverages, whole grain and coffee). In total, 25,069 individuals aged 45-74 years with genotype information and without prevalent diabetes from the Malmö Diet and Cancer cohort (1991-1996) were included. Diet data were collected with a modified diet history method. Results: During 17-year follow-up, 3588 incident T2D cases were identified. Both the diet risk score (HR in the highest risk category 1.40; 95% CI 1.26, 1.58; P trend=6×10-10) and the genetic risk score (HR in the highest tertile of the genetic risk score 1.67; 95% CI 1.54, 1.81; P trend=7×10-35) were associated with increased incidence of T2D. No significant interaction between the genetic risk score and the diet risk score (P=0.83) or its food components was observed. The highest risk was seen among the 6% of the individuals with both high genetic and dietary risk scores (HR 2.49; 95% CI 2.06, 3.01). Conclusions: The findings thus show that both genetic heredity and dietary habits previously associated with T2D add to the risk of T2D, but they seem to act in an independent fashion, with the consequence that all individuals, whether at high or low genetic risk, would benefit from favourable food choices.
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| 3. |
- Hellstrand, Sophie, et al.
(författare)
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Genetic susceptibility to dyslipidemia and incidence of cardiovascular disease depending on a diet quality index in the Malmö diet and cancer cohort
- 2016
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Ingår i: Genes & Nutrition. - : Springer Science and Business Media LLC. - 1555-8932 .- 1865-3499. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: By taking diet quality into account, we may clarify the relationship between genetically elevated triglycerides (TG) and low-density lipoprotein-cholesterol (LDL-C), and better understand the inconsistent results regarding genetically elevated high-density lipoprotein-cholesterol (HDL-C), and cardiovascular disease (CVD) risk. Methods: We included 24,799 participants (62 % women, age 44-74 years) from the Malmö Diet and Cancer cohort. During a mean follow-up time of 15 years, 3068 incident CVD cases (1814 coronary and 1254 ischemic stroke) were identified. Genetic risk scores (GRSs) were constructed by combining 80 validated genetic variants associated with higher TG and LDL-C or lower HDL-C. The participants’ dietary intake, assessed by a modified diet history method, was ranked according to a diet quality index that included six dietary components: saturated fat, polyunsaturated fat, fish, fiber, fruit and vegetables, and sucrose. Results: The GRSLDL-C (P=5×10-6) and GRSHDL-C (P = 0.02) but not GRSTG (P = 0.08) were significantly associated with CVD risk. No significant interaction between the GRSs and diet quality was observed on CVD risk (P > 0.39). A high compared to a low diet quality attenuated the association between GRSLDL-C and the risk of incident ischemic stroke (P interaction = 0.01). Conclusion: We found some evidence of an interaction between diet quality and GRSLDL-C on ischemic stroke.
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| 4. |
- Hindy, George, et al.
(författare)
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Several type 2 diabetes-associated variants in genes annotated to WNT signaling interact with dietary fiber in relation to incidence of type 2 diabetes
- 2016
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Ingår i: Genes & Nutrition. - : Springer Science and Business Media LLC. - 1555-8932 .- 1865-3499. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: TCF7L2 is a central transcription factor in the canonical wingless-type MMTV integration site (WNT) signaling pathway, and genetic variants in TCF7L2 have been found to interact with dietary fiber intake on type 2 diabetes risk. Here, we investigate whether other type 2 diabetes genes could be involved in the WNT signaling pathway and whether variants in such genes might interact with dietary fiber on type 2 diabetes incidence. Results: We included 26,905 individuals without diabetes from the Malmö Diet and Cancer Study cohort. Diet data was collected at baseline using a food frequency questionnaire, a 7-day food record, and an interview. Altogether, 51 gene loci were analyzed for putative links to WNT signaling. Over a mean follow-up period of 14.7 years, 3132 incident cases of type 2 diabetes were recorded. Seven genes (nine single nucleotide polymorphisms (SNPs)) were annotated as involved in WNT signaling including TCF7L2 (rs7903146 and rs12255372), HHEX (rs1111875), HNF1A (rs7957197), NOTCH2 (rs10923931), TLE4 (rs13292136), ZBED3 (rs4457053), and PPARG (rs1801282 and rs13081389). SNPs in TCF7L2, NOTCH2, and ZBED3 showed significant interactions with fiber intake on type 2 diabetes incidence (Pinteraction = 0.034, 0.005, 0.017, and 0.002, respectively). The magnitude of the association between the TCF7L2 risk allele and incident type 2 diabetes increased from the lowest to the highest quintiles of fiber intake. Higher fiber associated with lower type 2 diabetes risk only among risk allele carriers of the NOTCH2 variant and homozygotes of the risk allele of the ZBED3 variant. Conclusions: Our results suggest that several type 2 diabetes susceptibility SNPs in genes involved in WNT signaling may interact with dietary fiber intake on type 2 diabetes incidence.
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| 5. |
- Iacomino, G., et al.
(författare)
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Circulating microRNAs are associated with early childhood obesity: results of the I.Family Study
- 2019
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Ingår i: Genes and Nutrition. - : Springer Science and Business Media LLC. - 1555-8932 .- 1865-3499. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundNearly 10years ago, the World Health Organization reported the increasing prevalence of overweight and obesity worldwide as a challenge for public health due to the associated adverse consequences. Epidemiological studies established a firm relationship between an elevated body mass index and chronic conditions such as diabetes, dyslipidemia, hypertension, heart disease, non-alcoholic fatty liver disease, and some types of cancer. Omic studies demonstrated that microRNA (miRNA) profile changes in tissues correlate with a number of diseases, including obesity. Recent studies showed a remarkable stability of miRNAs also in blood, emphasizing their potential as theranostic agents for a variety of disorders and conditions. A number of miRNAs enriched in homeostasis of obesity and metabolic disorders have been characterized in previous researches.AimThis work was finalized to investigate the differential circulating miRNAs signature in early childhood obesity. Our cross-sectional study analyzed the signature of circulating miRNAs in plasma samples of normal weight (n=159) and overweight/obese (n=149) children and adolescents participating to the I.Family study, an EC-funded study finalized to investigate the etiology of overweight, obesity and related disorders and the determinants of food choice, lifestyle, and related health outcomes in children and adolescents of eight European countries (www.ifamilystudy.eu).ResultsDifferences in miRNA signature with respect to anthropometric and biochemical variables were analyzed. A high degree of variability in levels of circulating miRNAs was identified among children from different countries, in line with recent reports supporting the hypothesis that these molecules are likewise affected by environmental and lifestyle factors. A panel of miRNAs differentially expressed in overweight/low-grade obesity children was characterized (miR-551a and miR-501-5p resulted upregulated; miR-10b-5p, miR-191-3p, miR-215-5p, and miR-874-3p resulted downregulated). ROC curves were also constructed for experimentally confirmed miRNAs. Single miRNAs generally exhibited low AUC values with the highest values for miR-874-3p and miR-501-5p which in combination provided an interesting value (AUC=0.782). Pearson's analysis confirmed that miR-10b-5p, miR-215-5p, miR-501-5p, miR-551a, and miR-874-3p significantly correlated with BMI z-score. Molecular interactions of obesity-associated miRNAs were also predicted by bioinformatics tools.ConclusionsOur work showed that several circulating miRNAs are differentially represented in overweight/low-grade obesity children and adolescents. Although causal pathways cannot be firmly inferred, it is conceivable that circulating miRNAs may be new biomarkers of early childhood obesity.Trial registrationISRCTN, ISRCTN62310987. Registered 23/02/2018 - Retrospectively registered.
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| 6. |
- Iresjö, Britt-Marie, 1963, et al.
(författare)
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Estrogen biosynthesis in cultured skeletal muscle cells (L6) induced by amino acids
- 2019
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Ingår i: Genes & Nutrition. - : Springer Science and Business Media LLC. - 1865-3499 .- 1555-8932. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Background Previous investigations have indicated upregulation of gene expression in cellular pathways related to the biosynthesis of steroids in response to amino acids (AA) in skeletal muscle cells. This suggests AA as modulators of de novo synthesis of sex steroids for muscle growth and improved functional capacity. The aim of the present study was to investigate if increased availability of amino acids induced biosynthesis of sex steroids in skeletal muscles. Methods Confluent L6 muscle cells were cultured in media with various AA concentrations (0.3 or 9mM AA or 2.1mM branched-chain (BCAA) only), following pre-culture in serum-free medium. Sex steroids were quantified by gas chromatography-tandem mass spectrometry (GC-MS/MS). Mevalonate (diphospho-) decarboxylase enzyme (MVD) was quantified by Western blot. Results The experiments confirmed that estradiol and estrone increased in both L6 cell lysates and in conditioned media at the end of experiments on confluent cells, while progesterone or androgenic steroids were not detected in either cell lysates or culture media. Estradiol (+31±3%) and estrone (+18±4%) increased significantly in cells cultured at 9mM AA (p <0.001 vs. 0.3mM AA, n =10). Similarly, MVD protein increased at 9mM AA (p <0.001 vs. 0.3mM AA, n =17). An addition of BCAA alone to media increased MVD-protein levels to the same extent as all AA (p<0.01 vs. 0.3mM AA, n =3). Conclusion Female sex steroids and MVD enzyme production increased significantly in response to amino acid availability. The results indicate a role of amino acids as modulators of local muscle estrogen synthesis in muscle cells from rats at feeding.
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| 7. |
- Landberg, Rikard, 1981, et al.
(författare)
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Biomarkers of cereal food intake
- 2019
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Ingår i: Genes and Nutrition. - : Springer Science and Business Media LLC. - 1555-8932 .- 1865-3499. ; 14:1
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Forskningsöversikt (refereegranskat)abstract
- Background/objectives: Cereal foods are major contributors to the daily energy, protein, and dietary fiber intake all over the world. The role of cereals in human health is dependent on whether they are consumed as refined or whole grain and on cereal species. To unravel the underlying mechanisms of health effects attributed to specific cereal foods and to provide more precise dietary advice, there is a need for improved dietary assessment of whole-grain intake. Dietary biomarkers of specific cereals, different fractions or cereal-containing foods could offer such a possibility. The aim of this review was to summarize the current status on biomarkers of different cereals, fractions, and specific cereal foods. Subjects and methods: A literature review was conducted and putative biomarkers of different cereals and pseudo-cereals (wheat, oats, rye, barley, rice, and quinoa) as well as for different grain fractions (whole grain, refined grain, bran) and foods were summarized and discussed. Results: Several putative biomarkers have been suggested for different cereals, due to their unique presence in these grains. Among the biomarkers, odd-numbered alkylresorcinols are the most well-studied and -evaluated biomarkers and reflect whole-grain wheat and rye intake. Even-numbered alkylresorcinols have been suggested to reflect quinoa intake. Recent studies have also highlighted the potential of avenanthramides and avenacosides as specific biomarkers of oat intake, and a set of biomarkers have been suggested to reflect rice bran intake. However, there are yet no specific biomarkers of refined grains. Most biomarker candidates remain to be evaluated in controlled interventions and free-living populations before applied as biomarkers of intake in food and health studies. Conclusion: Several putative biomarkers of different cereals have been suggested and should be validated in human studies using recently developed food intake biomarker validation criteria.
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| 8. |
- Leder, Lena, et al.
(författare)
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Effects of a healthy Nordic diet on gene expression changes in peripheral blood mononuclear cells in response to an oral glucose tolerance test in subjects with metabolic syndrome : A SYSDIET sub-study
- 2016
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Ingår i: Genes & Nutrition. - : Springer Science and Business Media LLC. - 1555-8932 .- 1865-3499. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Diet has a great impact on the risk of developing features of metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), and cardiovascular diseases (CVD). We evaluated whether a long-term healthy Nordic diet (ND) can modify the expression of inflammation and lipid metabolism-related genes in peripheral blood mononuclear cells (PBMCs) during a 2-h oral glucose tolerance test (OGTT) in individuals with MetS. Methods: A Nordic multicenter randomized dietary study included subjects (n = 213) with MetS, randomized to a ND group or a control diet (CD) group applying an isocaloric study protocol. In this sub-study, we included subjects (n = 89) from three Nordic centers: Kuopio (n =26), Lund (n = 30), and Oulu (n = 33) with a maximum weight change of ±4 kg, high-sensitivity C-reactive protein concentration ≤10 mg L-1, and baseline body mass index -2. PBMCs were isolated, and the mRNA gene expression analysis was measured by quantitative real-time polymerase chain reaction (qPCR). We analyzed the mRNA expression changes of 44 genes before and after a 2hOGTT at the beginning and the end of the intervention. Results: The healthy ND significantly down-regulated the expression of toll-like receptor 4 (TLR4), interleukin 18 (IL18), and thrombospondin receptor (CD36) mRNA transcripts and significantly up-regulated the expression of peroxisome proliferator-activated receptor delta (PPARD) mRNA transcript after the 2hOGTT compared to the CD. Conclusions: A healthy ND is able to modify the gene expression in PBMCs after a 2hOGTT. However, more studies are needed to clarify the biological and clinical relevance of these findings.
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