Effect of Genotype and Maternal Affective Disorder on Intronic Methylation of FK506 Binding Protein 5 in Cord Blood DNA.

A single nucleotide polymorphism (SNP: rs1360780) in has been shown to interact with exposure to childhood adversity to promote loss of methylation and increase in gene expression in adults. We asked whether rs1360780 can influence intronic methylation in the context of exposure to maternal affective disorders . Sixty cord blood DNA samples from the Boston Birth Cohort were genotyped at rs1360780 and studied for methylation changes as they relate to genotype and exposure to affective disorders during pregnancy. Linear regression was employed to contrast the risk (TT) genotype to the heterozygous (CT) and homozygous (CC) genotypes with adjustment for potential confounders. The recessive genotype (TT) was associated with increased methylation at multiple CpGs in the intron 5 region ( < 0.01). These findings were enhanced among cases exposed to maternal affective disorders ( = 0.02). A human cell line treated with cortisol showed that changes in intron 5 CpG methylation and expression were inversely associated. These findings suggest that rs1360780 can influence intronic methylation by acting in as a methylation quantitative locus and highlight the impact of genotypic risk on methylation . Additionally, prenatal stress exposure compounded with the risk genotype may lead to a compensatory increase in methylation.