Global maternal early pregnancy peripheral blood mRNA and miRNA expression profiles according to plasma 25-hydroxyvitamin D concentrations

Abstract

Objective. We investigated associations of early pregnancy maternal vitamin D concentrations with differential gene expression and post-transcription regulation.

Method. Plasma 25-hydroxyvitamin D (25[OH]D) was measured among participants of a nested case–control study. Participants with low (<25.5 ng/ml) and high (≥31.7 ng/ml) 25[OH]D were identified among controls. Peripheral blood messenger RNA (mRNA) (N = 21) and microRNA (miRNA) (N = 13) expression studies were conducted among participants with low and high 25[OH]D concentrations. Differential expression between low/high groups were evaluated using Student's t-test, fold change, and SAM comparisons. We further investigated functions and functional relationships of differentially expressed mRNAs and targets of differentially expressed miRNAs.

Results. Three hundred and five genes (299 upregulated and 6 downregulated) and 11 miRNAs (10 downregulated and 1 upregulated) were differentially expressed among participants with low 25[OH]D compared with those who had high 25[OH]D. Genes that participate in a wide range of cellular functions, including organ and system development (e.g. angiogenesis), inflammation and metabolic processes (e.g. carbohydrate/lipid metabolism), as well as miRNAs that target these genes were differentially expressed among women with low 25[OH]D compared with those with high 25[OH]D.

Conclusion. Early pregnancy plasma 25[OH]D concentrations are associated with maternal peripheral blood gene expression and post-transcription regulation.

Keywords:

• Vitamin D
• transcription
• post-transcription regulation
• microarray
• early pregnancy
• whole blood

Acknowledgments

We are indebted to the participants of the Omega study for their cooperation. They are also grateful for the technical expertise of staff of the Center for Perinatal Studies, Swedish Medical Center. This work was supported by grants from the National Institute of Child Health and Human Development, National Institutes of Health (HD/HL R01-32562) and the March of Dimes (#1 FY08-425).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.