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Genetic variation in the vitamin D receptor (VDR) and the plasma proteome
Author(s) -
Bailo Bibiana Garcia,
Badawi Alaa,
El-Sohemy Ahmed
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1012.6
Subject(s) - calcitriol receptor , vitamin d and neurology , vitamin d binding protein , foki , vitamin , biology , endocrinology , genetic variation , medicine , genetics , gene , polymorphism (computer science) , genotype
Vitamin D deficiency has been linked to numerous diseases. 1,25(OH) 2 D, the active vitamin D form, binds to the nuclear vitamin D receptor (VDR) and affects target gene expression in multiple pathways. However, it is not known if genetic variants in VDR affect plasma protein levels. The objective was to explore associations between VDR variants and 54 plasma proteins belonging to disease‐associated pathways in healthy young adults (n=488). 16 genetic variants across VDR were extracted from genome‐wide data available for the study cohort. Protein concentrations were measured by a multiple reaction monitoring HPLC‐MS/MS assay. Associations between proteins and variants were explored by linear regression with an additive inheritance mode. We found 32 significant associations. The strongest association ( p =5.06×10 −5 ) was observed between rs2283342 and inter‐α‐trypsin inhibitor HC (IT) ( r 2 =0.03, β= −0.03±0.01), a serine protease inhibitor involved in inflammation. We then examined whether serum 25(OH)D, a marker of vitamin D status, affected any associations. 25(OH)D modified the association between rs2283342 and IT, as well as associations between rs2228570 ( Fok1 ) and several apolipoproteins. These results suggest a role for vitamin D in disease associated pathways such as inflammation and lipid metabolism. Research support from the Advanced Foods and Materials Network.Grant Funding Source : Advanced Foods and Materials Network