| Autor: |
Colin, E M, Weel, A E, Uitterlinden, A G, Buurman, C J, Birkenhäger, J C, Pols, H A, van Leeuwen, J P |
| Přispěvatelé: |
Internal Medicine, Epidemiology |
| Jazyk: |
angličtina |
| Rok vydání: |
2000 |
| Zdroj: |
Clinical Endocrinology, 52(2), 211-216. Wiley-Blackwell Publishing Ltd |
| ISSN: |
0300-0664 |
| Popis: |
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)2D3 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)2D3. DESIGN: PBMC of women were isolated, VDR genotyped and in vitro inhibition by 1,25-(OH)2D3 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 ED50 than the Ff genotype corresponding to an allele dose effect of 0.32 nM per f allele copy (P = 0.0036). For BsmI genotypes no differences in ED50 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)2D3. Especially under conditions of vitamin D insufficiency these findings might have clinical implications. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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