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DOI10.1371/journal.pone.0159779
Mapping Variation in Cellular and Transcriptional Response to 1,25-Dihydroxyvitamin D3 in Peripheral Blood Mononuclear Cells
Kariuki, Silvia N.1; Maranville, Joseph C.1,3; Baxter, Shaneen S.1,4; Jeong, Choongwon1; Nakagome, Shigeki1; Hrusch, Cara L.2; Witonsky, David B.1; Sperling, Anne I.2; Di Rienzo, Anna1
通讯作者Di Rienzo, Anna
来源期刊PLOS ONE
ISSN1932-6203
出版年2016
卷号11期号:7
英文摘要

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


类型Article
语种英语
国家USA
收录类别SCI-E
WOS记录号WOS:000381515200044
WOS关键词SYSTEMIC-LUPUS-ERYTHEMATOSUS ; GENOME-WIDE ASSOCIATION ; REGULATORY T-CELLS ; VITAMIN-D ; MULTIPLE-SCLEROSIS ; CHIP-SEQ ; 1-ALPHA,25-DIHYDROXYVITAMIN D-3 ; CONTROLLED-TRIAL ; BINDING-PROTEIN ; IMMUNE-SYSTEM
WOS类目Multidisciplinary Sciences
WOS研究方向Science & Technology - Other Topics
来源机构Arizona State University
资源类型期刊论文
条目标识符http://119.78.100.177/qdio/handle/2XILL650/195646
作者单位1.Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA;
2.Univ Chicago, Dept Med, 5841 S Maryland Ave, Chicago, IL 60637 USA;
3.Merck Res Labs, Boston, MA USA;
4.Univ Maryland, Sch Med, Ctr Vasc & Inflammatory Dis, Baltimore, MD 21201 USA
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Kariuki, Silvia N.,Maranville, Joseph C.,Baxter, Shaneen S.,et al. Mapping Variation in Cellular and Transcriptional Response to 1,25-Dihydroxyvitamin D3 in Peripheral Blood Mononuclear Cells[J]. Arizona State University,2016,11(7).
APA Kariuki, Silvia N..,Maranville, Joseph C..,Baxter, Shaneen S..,Jeong, Choongwon.,Nakagome, Shigeki.,...&Di Rienzo, Anna.(2016).Mapping Variation in Cellular and Transcriptional Response to 1,25-Dihydroxyvitamin D3 in Peripheral Blood Mononuclear Cells.PLOS ONE,11(7).
MLA Kariuki, Silvia N.,et al."Mapping Variation in Cellular and Transcriptional Response to 1,25-Dihydroxyvitamin D3 in Peripheral Blood Mononuclear Cells".PLOS ONE 11.7(2016).
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