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Genetic control of serum 1,25 dihydroxyvitamin D (1,25D) level under normal and low dietary calcium (Ca) conditions
Author(s) -
Replogle Rebecca A,
Wang Libo,
Zhang Min,
Fleet James C.
Publication year - 2013
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.27.1_supplement.1057.17
Subject(s) - quantitative trait locus , calcitriol receptor , heritability , vitamin d and neurology , genetic variation , endocrinology , candidate gene , medicine , biology , allele , inbred strain , gene , genetics
Low dietary Ca intake increases renal conversion of 25 hydroxyvitamin D (25D) to 1,25D. This adaptation protects bone under periods of dietary Ca stress. We conducted two studies to characterize the genetic controls on serum 25D and 1,25D levels in mice. Male mice from 11 inbred lines (Study 1) and 51 BXD recombinant inbred lines (Study 2) were placed on diets containing 200 IU vitamin D and either normal (0.5%) or low (0.25%) Ca from 4–12 wks of age. Study 1 revealed significant variation in serum 25D, serum 1,25D, and adaptation of serum 1,25D to low dietary Ca intake among the 11 lines. In Study 2, narrow sense heritability (h 2 ) of 25D and 1,25D on the 0.5% Ca diet was 0.40 and 0.66, respectively. Quantitative trait loci (QTL) were located using composite interval mapping (CIM) and a Bayesian method. Five loci were in common between metabolites. Twelve QTL affecting 25D were identified and included the candidate genes VDR, Cdh3, and FGF23 located near the QTL on chr 6, 8, and 15. Nineteen QTL accounting for 52% of the genetic variance in 1,25D were identified, including 3 diet interaction loci. Previously identified candidate genes are near 5 loci, including the VDR gene. Our results show serum vitamin D metabolite levels are controlled by multiple genetic factors that, in some cases, interact with the dietary environment. Supported by NIH awards ES019103 to JCF and USDA NIFA award 2012–67011‐19963 to RAR