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Haplotypes defined by promoter and intron 1 polymorphisms of the COLIA1 gene regulate bone mineral density in women

Stewart, Tracy L ; Jin, Huilin ; McGuigan, Fiona LU ; Albagha, Omar M E ; Garcia-Giralt, Natalia ; Bassiti, Amelia ; Grinberg, Daniel ; Balcells, Susana ; Reid, David M and Ralston, Stuart H (2006) In Journal of Clinical Endocrinology and Metabolism 91(9). p.3575-3583
Abstract
CONTEXT: The COLIA1 gene is a strong candidate for susceptibility to osteoporosis. The causal genetic variants are currently unclear, but the most likely are functional polymorphisms in the promoter and intron 1 of COLIA1. OBJECTIVE: The objective of the study was to determine whether promoter and intron 1 polymorphisms of COLIA1 or haplotypes defined by these polymorphisms regulate bone mineral density (BMD) in women. DESIGN: This was a population-based association study involving 3270 women from the United Kingdom who took part in a regional osteoporosis screening program. MAIN OUTCOME MEASURES: BMD at the lumbar spine (LS-BMD) and femoral neck (FN-BMD) was measured on two occasions approximately 6 yr apart, in relation to polymorphisms... (More)
CONTEXT: The COLIA1 gene is a strong candidate for susceptibility to osteoporosis. The causal genetic variants are currently unclear, but the most likely are functional polymorphisms in the promoter and intron 1 of COLIA1. OBJECTIVE: The objective of the study was to determine whether promoter and intron 1 polymorphisms of COLIA1 or haplotypes defined by these polymorphisms regulate bone mineral density (BMD) in women. DESIGN: This was a population-based association study involving 3270 women from the United Kingdom who took part in a regional osteoporosis screening program. MAIN OUTCOME MEASURES: BMD at the lumbar spine (LS-BMD) and femoral neck (FN-BMD) was measured on two occasions approximately 6 yr apart, in relation to polymorphisms and haplotypes defined by polymorphisms within the COLIA1 intron 1 (+1245G/T; rs1800012) and promoter (-1997G/T; rs1107946; -1663IndelT; rs2412298). RESULTS: The polymorphisms were in strong linkage disequilibrium, and three haplotypes accounted for more than 95% of alleles at the COLIA1 locus. The individual polymorphisms were associated with BMD, but the most consistent associations were with haplotypes defined by all three polymorphisms. Homozygote carriers of haplotype 2 (-1997G/-1663delT/+1245T) had reduced BMD at baseline (P = 0.007 for LS-BMD; P = 0.008 for FN-BMD), whereas homozygotes for haplotype 3 (-1997T/-1663insT/+1245G) had increased BMD (P = 0.007 for LS-BMD). Similar associations were observed at follow-up for haplotype 3, but the association with haplotype 2 was weaker due to increased uptake of hormone replacement therapy in homozygotes for this haplotype. CONCLUSIONS: Two haplotypes defined by polymorphisms in the 5' flank of the COLIA1 regulate BMD in a bidirectional manner in women. (Less)
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publishing date
type
Contribution to journal
publication status
published
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in
Journal of Clinical Endocrinology and Metabolism
volume
91
issue
9
pages
3575 - 3583
publisher
Oxford University Press
external identifiers
  • pmid:16804049
  • scopus:33748697577
ISSN
1945-7197
DOI
10.1210/jc.2005-2651
language
English
LU publication?
yes
id
218bd4d6-377d-4d5f-a4db-0a19e98941f0 (old id 1136335)
date added to LUP
2016-04-01 16:08:26
date last changed
2020-06-10 03:48:51
@article{218bd4d6-377d-4d5f-a4db-0a19e98941f0,
  abstract     = {CONTEXT: The COLIA1 gene is a strong candidate for susceptibility to osteoporosis. The causal genetic variants are currently unclear, but the most likely are functional polymorphisms in the promoter and intron 1 of COLIA1. OBJECTIVE: The objective of the study was to determine whether promoter and intron 1 polymorphisms of COLIA1 or haplotypes defined by these polymorphisms regulate bone mineral density (BMD) in women. DESIGN: This was a population-based association study involving 3270 women from the United Kingdom who took part in a regional osteoporosis screening program. MAIN OUTCOME MEASURES: BMD at the lumbar spine (LS-BMD) and femoral neck (FN-BMD) was measured on two occasions approximately 6 yr apart, in relation to polymorphisms and haplotypes defined by polymorphisms within the COLIA1 intron 1 (+1245G/T; rs1800012) and promoter (-1997G/T; rs1107946; -1663IndelT; rs2412298). RESULTS: The polymorphisms were in strong linkage disequilibrium, and three haplotypes accounted for more than 95% of alleles at the COLIA1 locus. The individual polymorphisms were associated with BMD, but the most consistent associations were with haplotypes defined by all three polymorphisms. Homozygote carriers of haplotype 2 (-1997G/-1663delT/+1245T) had reduced BMD at baseline (P = 0.007 for LS-BMD; P = 0.008 for FN-BMD), whereas homozygotes for haplotype 3 (-1997T/-1663insT/+1245G) had increased BMD (P = 0.007 for LS-BMD). Similar associations were observed at follow-up for haplotype 3, but the association with haplotype 2 was weaker due to increased uptake of hormone replacement therapy in homozygotes for this haplotype. CONCLUSIONS: Two haplotypes defined by polymorphisms in the 5' flank of the COLIA1 regulate BMD in a bidirectional manner in women.},
  author       = {Stewart, Tracy L and Jin, Huilin and McGuigan, Fiona and Albagha, Omar M E and Garcia-Giralt, Natalia and Bassiti, Amelia and Grinberg, Daniel and Balcells, Susana and Reid, David M and Ralston, Stuart H},
  issn         = {1945-7197},
  language     = {eng},
  number       = {9},
  pages        = {3575--3583},
  publisher    = {Oxford University Press},
  series       = {Journal of Clinical Endocrinology and Metabolism},
  title        = {Haplotypes defined by promoter and intron 1 polymorphisms of the COLIA1 gene regulate bone mineral density in women},
  url          = {http://dx.doi.org/10.1210/jc.2005-2651},
  doi          = {10.1210/jc.2005-2651},
  volume       = {91},
  year         = {2006},
}