A genome-wide methylation study of severe vitamin D deficiency in African American adolescents.
J Pediatr
; 162(5): 1004-9.e1, 2013 May.
Article
em En
| MEDLINE
| ID: mdl-23219444
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. STUDYDESIGN:
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Vitamina D
/
Deficiência de Vitamina D
/
Metilação de DNA
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
/
Adult
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Humans
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Male
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article