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Genes in white blood cells of blacks associated with vitamin D deficiency – May 2013

A Genome-Wide Methylation Study of Severe Vitamin D Deficiency in African American Adolescents

The Journal of Pediatrics. Volume 162, Issue 5 , Pages 1004-1009.e1, May 2013
Haidong Zhu, MD, PhD email address , Xiaoling Wang, MD, PhD , Huidong Shi, PhD ,
Shaoyong Su, PhD , Gregory A. Harshfield, PhD , Bernard Gutin, PhD , Harold Snieder, PhD , Yanbin Dong, MD, PhD
Received 2 July 2012; received in revised form 13 September 2012; accepted 31 October 2012. published online 10 December 2012.

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.

See also VitaminDWiki


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