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Plasma 25 hydroxyvitamin D level and blood gene expression profiles: a cross-sectional study of the Norwegian Women and Cancer Post-genome Cohort.

ABSTRACT: Vitamin D deficiency has been associated with increased risk of developing several diseases, but much is unknown about the molecular effects involved. Gene expression technology is increasingly being used to elucidate molecular mechanisms related to nutritional factors, and in this study of free-living, middle-aged Norwegian women, we aimed at identifying gene expression pathways in the blood associated with vitamin D status.Blood samples and questionnaires were collected as a part of the Norwegian Women and Cancer Post-genome Cohort (500 invited subjects, 218 included). Plasma 25 hydroxyvitamin D (25(OH)D) concentrations were measured using high-performance liquid chromatography, and we compared groups with sufficient versus deficient vitamin D status (25(OH)D >50?nmol/l (n=66) versus <37.5?nmol/l (n=83)), to identify differences in gene expression profiles obtained using full-genome microarrays.In a targeted pathway-level analysis, several immunological processes, immune cell functions and major signaling pathways were differentially regulated according to vitamin D status (P<0.01). To a certain degree, results from in vitro studies reported in the literature were reflected in this population setting.We conclude that vitamin D status measured as 25(OH)D was associated with molecular pathways that may ultimately affect the potential onset of diseases. The use of gene expression analysis in a population setting may give valuable input to the study of effects of nutritional factors.

SUBMITTER: Standahl Olsen K

PROVIDER: S-EPMC3701290 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Plasma 25 hydroxyvitamin D level and blood gene expression profiles: a cross-sectional study of the Norwegian Women and Cancer Post-genome Cohort.

Standahl Olsen K K Rylander C C Brustad M M Aksnes L L Lund E E

European journal of clinical nutrition 20130306 7

<h4>Background/objectives</h4>Vitamin D deficiency has been associated with increased risk of developing several diseases, but much is unknown about the molecular effects involved. Gene expression technology is increasingly being used to elucidate molecular mechanisms related to nutritional factors, and in this study of free-living, middle-aged Norwegian women, we aimed at identifying gene expression pathways in the blood associated with vitamin D status.<h4>Subjects/methods</h4>Blood samples an ...[more]

PMID: 23462941

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Project description:High blood concentrations of n-6 fatty acids (FAs) relative to n-3 FAs may lead to a "physiological switch" towards permanent low-grade inflammation, potentially influencing the onset of cardiovascular and inflammatory diseases, as well as cancer. To explore the potential effects of FA ratios prior to disease onset, we measured blood gene expression profiles and plasma FA ratios (linoleic acid/alpha-linolenic acid, LA/ALA; arachidonic acid/eicosapentaenoic acid, AA/EPA; and total n-6/n-3) in a cross-section of middle-aged Norwegian women (n = 227). After arranging samples from the highest values to the lowest for all three FA ratios (LA/ALA, AA/EPA and total n-6/n-3), the highest and lowest deciles of samples were compared. Differences in gene expression profiles were assessed by single-gene and pathway-level analyses. The LA/ALA ratio had the largest impact on gene expression profiles, with 135 differentially expressed genes, followed by the total n-6/n-3 ratio (125 genes) and the AA/EPA ratio (72 genes). All FA ratios were associated with genes related to immune processes, with a tendency for increased pro-inflammatory signaling in the highest FA ratio deciles. Lipid metabolism related to peroxisome proliferator-activated receptor γ (PPARγ) signaling was modified, with possible implications for foam cell formation and development of cardiovascular diseases. We identified higher expression levels of several autophagy marker genes, mainly in the lowest LA/ALA decile. This finding may point to the regulation of autophagy as a novel aspect of FA biology which warrants further study. Lastly, all FA ratios were associated with gene sets that included targets of specific microRNAs, and gene sets containing common promoter motifs that did not match any known transcription factors. We conclude that plasma FA ratios are associated with differences in blood gene expression profiles in this free-living population, and that affected genes and pathways may influence the onset and progression of disease.

Project description:Laboratory studies suggest that vitamin D may inhibit pancreatic cancer cell growth. However, epidemiologic studies of vitamin D and pancreatic cancer risk have been conflicting.To determine whether prediagnostic levels of plasma 25-hydroxyvitamin D (25[OH]D; IDS Inc.; enzyme immunoassay) were associated with risk of pancreatic cancer, we conducted a pooled analysis of nested case-control studies with 451 cases and 1,167 controls from five cohorts through 2008. Median follow-up among controls was 14.1 years in Health Professionals Follow-Up Study (HPFS), 18.3 years in Nurses' Health Study (NHS), 25.3 years in Physicians' Health Study (PHS), 12.2 years in Women's Health Initiative-Observational Study (WHI), and 14.4 years in Women's Health Study (WHS). Logistic regression was used to compare the odds of pancreatic cancer by plasma level of 25(OH)D.Mean plasma 25(OH)D was lower in cases versus controls (61.3 vs. 64.5 nmol/L, P = 0.005). In logistic regression models, plasma 25(OH)D was inversely associated with odds of pancreatic cancer. Participants in quintiles two through five had multivariable-adjusted ORs (95% confidence intervals) of 0.79 (0.56-1.10), 0.75 (0.53-1.06), 0.68 (0.48-0.97), and 0.67 (0.46-0.97; P(trend) = 0.03), respectively, compared with the bottom quintile. Compared with those with insufficient levels [25[OH]D, <50 nmol/L], ORs were 0.75 (0.58-0.98) for subjects with relative insufficiency [25[OH]D, 50 to <75 nmol/L] and 0.71 (0.52-0.97) for those with sufficient levels [25[OH]D, ? 75 nmol/L]. No increased risk was noted in subjects with 25(OH)D ?100 nmol/L, as suggested in a prior study. In subgroup analyses, ORs for the top versus bottom quartile of 25(OH)D were 0.72 (0.48-1.08) for women, 0.73 (0.40-1.31) for men, and 0.73 (0.51-1.03) for Whites.Among participants in five large prospective cohorts, higher plasma levels of 25(OH)D were associated with a lower risk for pancreatic cancer.Low circulating 25(OH)D may predispose individuals to the development of pancreatic cancer.

Dataset Information

Plasma 25 hydroxyvitamin D level and blood gene expression profiles: a cross-sectional study of the Norwegian Women and Cancer Post-genome Cohort.

Publications

Plasma 25 hydroxyvitamin D level and blood gene expression profiles: a cross-sectional study of the Norwegian Women and Cancer Post-genome Cohort.

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