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

Tracy L. Stewart, Huilin Jin, Fiona E A McGuigan, Omar Al Bagha, Natalia Garcia-Giralt, Amelia Bassiti, Daniel Grinberg, Susana Balcells, David M. Reid, Stuart H. Ralston

Research output: Contribution to journalArticle

44 Citations (Scopus)

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: BMDat 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.

Original languageEnglish
Pages (from-to)3575-3583
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume91
Issue number9
DOIs
Publication statusPublished - 2006
Externally publishedYes

Fingerprint

Polymorphism
Bone Density
Introns
Haplotypes
Minerals
Bone
Genes
Homozygote
Osteoporosis
Femur Neck
Hormone Replacement Therapy
Linkage Disequilibrium
Screening
Spine
Alleles
Outcome Assessment (Health Care)
Hormones

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

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 E A; Al Bagha, Omar; Garcia-Giralt, Natalia; Bassiti, Amelia; Grinberg, Daniel; Balcells, Susana; Reid, David M.; Ralston, Stuart H.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 91, No. 9, 2006, p. 3575-3583.

Research output: Contribution to journalArticle

Stewart, TL, Jin, H, McGuigan, FEA, Al Bagha, O, Garcia-Giralt, N, Bassiti, A, Grinberg, D, Balcells, S, Reid, DM & Ralston, SH 2006, 'Haplotypes defined by promoter and intron 1 polymorphisms of the COLIA1 gene regulate bone mineral density in women', Journal of Clinical Endocrinology and Metabolism, vol. 91, no. 9, pp. 3575-3583. https://doi.org/10.1210/jc.2005-2651
Stewart, Tracy L. ; Jin, Huilin ; McGuigan, Fiona E A ; Al Bagha, Omar ; Garcia-Giralt, Natalia ; Bassiti, Amelia ; Grinberg, Daniel ; Balcells, Susana ; Reid, David M. ; Ralston, Stuart H. / Haplotypes defined by promoter and intron 1 polymorphisms of the COLIA1 gene regulate bone mineral density in women. In: Journal of Clinical Endocrinology and Metabolism. 2006 ; Vol. 91, No. 9. pp. 3575-3583.
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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: BMDat 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 Huilin Jin and McGuigan, {Fiona E A} and {Al Bagha}, Omar and Natalia Garcia-Giralt and Amelia Bassiti and Daniel Grinberg and Susana Balcells and Reid, {David M.} and Ralston, {Stuart H.}",
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T1 - Haplotypes defined by promoter and intron 1 polymorphisms of the COLIA1 gene regulate bone mineral density in women

AU - Stewart, Tracy L.

AU - Jin, Huilin

AU - McGuigan, Fiona E A

AU - Al Bagha, Omar

AU - Garcia-Giralt, Natalia

AU - Bassiti, Amelia

AU - Grinberg, Daniel

AU - Balcells, Susana

AU - Reid, David M.

AU - Ralston, Stuart H.

PY - 2006

Y1 - 2006

N2 - 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: BMDat 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.

AB - 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: BMDat 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.

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