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. 2013 May;162(5):1004-9.e1.
doi: 10.1016/j.jpeds.2012.10.059. Epub 2012 Dec 7.

A genome-wide methylation study of severe vitamin D deficiency in African American adolescents

Haidong Zhu  1 , Xiaoling Wang, Huidong Shi, Shaoyong Su, Gregory A Harshfield, Bernard Gutin, Harold Snieder, Yanbin Dong
Affiliations

A genome-wide methylation study of severe vitamin D deficiency in African American adolescents

Haidong Zhu et al. J Pediatr. 2013 May.

Abstract

Objectives: To test the hypothesis that changes in DNA methylation are involved in vitamin D deficiency-related immune cell regulation using an unbiased genome-wide approach combined with a genomic and epigenomic integrative approach.

Study design: We performed a genome-wide methylation scan using the Illumina HumanMethylation 27 BeadChip on leukocyte DNA of 11 cases of vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D] ≤ 25 nmol/L) and 11 age-matched controls ([25(OH)D] > 75 nmol/L); the subjects were African American normal-weight (body mass index <85th percentile) males aged 14-19 years. The Limma package was used to analyze each CpG site for differential methylation between cases and controls. To correct for multiple testing, the set of raw P values were converted to false discovery rates (FDRs). We also compared our findings with the recent data from Genome-Wide Association Studies of circulating 25(OH)D levels and then performed a permutation test to examine whether the "double hit" genes were randomly enriched.

Results: A total of 79 CpG sites achieved raw P < .001. Of the 79 CpG sites, 2 CpG sites survived multiple testing: cg16317961 (raw P = 3.5 × 10(-6), FDR = 0.078, in MAPRE2) and cg04623955 (raw P = 5.9 × 10(-6), FDR = 0.078, in DIO3). Furthermore, 3 out of the 4 genes previously identified in the 2 Genome-Wide Association Studies were also significant at the methylation level (DHCR7: cg07487535, P = .015 and cg10763288, P = .017; CYP2R1: cg25454890, P = .040; CYP24A1: cg18956481, P = .022), reflecting significant enrichment (P = .0098).

Conclusion: Severe vitamin D deficiency is associated with methylation changes in leukocyte DNA. The genomic and epigenomic approach reinforce the crucial roles played by the DHCR7, CYP2R1, and CYP24A1 genes in vitamin D metabolism.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Legend: Volcano plot showing raw p-values versus mean methylation differences between severe vitamin D deficient cases and matched controls.
See this image and copyright information in PMC

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