Mapping Variation in Cellular and Transcriptional Response to 1,25-Dihydroxyvitamin D3 in Peripheral Blood Mononuclear Cells.

摘要: The active hormonal form of vitamin D, 1,25-dihydroxyvitamin D (1,25D) is an important modulator the immune system, inhibiting cellular proliferation and regulating transcription response genes. In order to characterize genetic basis variation in immunomodulatory effects 1,25D, we mapped quantitative traits 1,25D at both transcriptional level. We carried out a genome-wide association scan percent inhibition cell (Imax) induced by treatment peripheral blood mononuclear cells from 88 healthy African-American individuals. Two significant variants were identified: rs1893662 gene desert on chromosome 18 (p = 2.32 x 10-8) rs6451692 5 2.55 10-8), which may influence anti-proliferative activity expression nearby genes such as chemokine gene, CCL28, translation initiation PAIP1. also identified 8 trait loci FDR<0.10 for treatment, include regulator ets variant 3-like (ETV3L) EH-domain containing 4 (EHD4). addition, eQTLs receptor binding sites near differentially expressed FERM Domain Containing 6 (FRMD6), plays critical role apoptosis. Combining information GWAS Imax eQTL mapping enabled identification putative Imax-associated candidate PAIP1 repressor ZNF649. Overall, this study are strong candidates diseases linked multiple sclerosis.