PMID- 16210379
OWN - NLM
STAT- MEDLINE
DCOM- 20060203
LR  - 20220330
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 14
IP  - 22
DP  - 2005 Nov 15
TI  - Two single-nucleotide polymorphisms in the human vitamin D receptor promoter 
      change protein-DNA complex formation and are associated with height and vitamin D 
      status in adolescent girls.
PG  - 3539-48
AB  - Numerous association studies have dealt with single-nucleotide polymorphisms 
      (SNPs) in coding and intronic regions of the human vitamin D receptor (hVDR) 
      gene. We have hypothesized that phenotypic traits may also be associated with 
      variations in VDR expression due to the presence of SNPs in promoter regions. In 
      this work, we have studied two SNPs located 1521 bp (G/C) and 1012 bp (A/G) 
      upstream of the transcriptional start site of the main human VDR gene promoter. 
      One base-change in any of the two variant sites led to a dramatic change in 
      protein-DNA complex formation using nuclear extracts from HEK293, Caco-2 and 
      COS-7 cells. Genetic analysis of 185 healthy adolescent girls evidenced two major 
      haplotypes: 1521G/1012A and 1521C/1012G and three main genotypes: homozygous for 
      1521G/1012A (21.1%), homozygous for 1521C/1012G (17.3%) and heterozygous 
      1521CG/1012GA (57.3%). On the basis of transfection data, promoter activity was 
      nearly 2-fold higher with the 1521G/1012A haplotype, when compared with the 
      1521C/1012G haplotype. Clinical and biological association study in the 
      adolescent cohort showed that girls with a CC/GG genotype had (i) lower 
      circulating levels of 25-dihydroxyvitamin D, with no detectable consequence on 
      calcium metabolism, (ii) lower serum IGF-1 levels and (iii) smaller height from 
      11 years of age up to adult height.
FAU - d'Alesio, Arnold
AU  - d'Alesio A
AD  - Inserm U561, Hopital Saint Vincent de Paul, Paris, France.
FAU - Garabedian, Michele
AU  - Garabedian M
FAU - Sabatier, Jean Pierre
AU  - Sabatier JP
FAU - Guaydier-Souquieres, Genevieve
AU  - Guaydier-Souquieres G
FAU - Marcelli, Christian
AU  - Marcelli C
FAU - Lemacon, Audrey
AU  - Lemacon A
FAU - Walrant-Debray, Odile
AU  - Walrant-Debray O
FAU - Jehan, Frederic
AU  - Jehan F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20051006
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (Transcription Factors)
RN  - 1406-16-2 (Vitamin D)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 9007-49-2 (DNA)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adolescent
MH  - Animals
MH  - Body Height/*genetics
MH  - Bone Development/genetics
MH  - COS Cells
MH  - Calcium/metabolism
MH  - Chlorocebus aethiops
MH  - DNA/*metabolism
MH  - Female
MH  - Haplotypes
MH  - Humans
MH  - Insulin-Like Growth Factor I/metabolism
MH  - Polymorphism, Single Nucleotide
MH  - *Promoter Regions, Genetic
MH  - Receptors, Calcitriol/*genetics/metabolism
MH  - Sequence Analysis, DNA
MH  - Transcription Factors/*metabolism
MH  - Vitamin D/*blood
EDAT- 2005/10/08 09:00
MHDA- 2006/02/04 09:00
CRDT- 2005/10/08 09:00
PHST- 2005/10/08 09:00 [pubmed]
PHST- 2006/02/04 09:00 [medline]
PHST- 2005/10/08 09:00 [entrez]
AID - ddi382 [pii]
AID - 10.1093/hmg/ddi382 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2005 Nov 15;14(22):3539-48. doi: 10.1093/hmg/ddi382. Epub 2005 Oct 
      6.