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Consequences of vitamin D receptor gene polymorphisms for growth inhibition of cultured human peripheral blood mononuclear cells by 1,25‐dihydroxyvitamin D 3
Author(s) -
Colin Edgar M.,
Weel Angelique E. A. M.,
Uitterlinden André G.,
Buurman Cok J.,
Birkenhäger Jan C.,
Pols Huibert A. P.,
Van Leeuwen Johannes P. T. M.
Publication year - 2000
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1046/j.1365-2265.2000.00909.x
Subject(s) - calcitriol receptor , foki , genotype , biology , endocrinology , medicine , peripheral blood mononuclear cell , allele , restriction fragment length polymorphism , vitamin d and neurology , polymorphism (computer science) , microbiology and biotechnology , gene , genetics , in vitro
OBJECTIVE In the vitamin D receptor (VDR) gene a BsmI restriction fragment length polymorphism (RFLP) in intron 8 and a translational start‐site polymorphism, identified as a FokI RFLP, have been described. Crucial for a proper interpretation of these polymorphisms in association studies is the knowledge whether they have direct consequences for 1,25‐(OH) 2 D 3 action at cellular level. The present study was designed to assess functional significance of the FokI and BsmI VDR gene polymorphisms in peripheral blood mononuclear cells (PBMC) with a natural occurring VDR genotype for cell growth inhibition by 1,25‐(OH) 2 D 3 . DESIGN PBMC of women were isolated, VDR genotyped and in vitro inhibition by 1,25‐(OH) 2 D 3 of Phytohemagglutinin (PHA)‐stimulated growth of PBMC was examined in relation to VDR genotype. RESULTS PHA‐stimulated growth and maximal growth inhibition were independent of VDR genotype. However, the FF genotype had a significant lower ED 50 than the Ff genotype corresponding to an allele dose effect of 0.32 n m per f allele copy ( P = 0.0036). For BsmI genotypes no differences in ED 50 were observed. CONCLUSION The present study demonstrates for the first time in cells with a natural VDR genotype a direct functional consequence of the VDR gene translational start‐site polymorphism for the action of 1,25‐(OH) 2 D 3 . Especially under conditions of vitamin D insufficiency these findings might have clinical implications.