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Osteoporosis International

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01-03-2011 | Original Article

Polymorphisms in the 5′ flank of COL1A1 gene and osteoporosis: meta-analysis of published studies

Authors: H. Jin, E. Evangelou, J. P. A. Ioannidis, S. H. Ralston

Published in: Osteoporosis International | Issue 3/2011

Abstract

Summary

A meta-analysis of studies was conducted involving 24,511 participants with 7,864 fractures in which polymorphisms in the 5′ flank of COL1A1 (rs1107946, rs2412298, and rs1800012) were related to osteoporosis phenotypes. Polymorphisms of all three sites were associated with BMD, and rs1800012 was associated with fracture but effect sizes were modest.

Introduction and hypothesis

Polymorphisms in the 5′ flank of COL1A1 gene have been implicated as genetic markers for susceptibility to osteoporosis, but previous studies have yielded conflicting results.

Methods

We conducted a meta-analysis of 32 studies including 24,511 participants and 7,864 fractures in which alleles at the -1997G/T (rs1107946), -1663in/delT (rs2412298), and Sp1 binding site polymorphisms (rs1800012) of COL1A1 had been related to bone mineral density (BMD) or fracture.

Results

For the Sp1 polymorphism, BMD values in TT homozygotes were 0.13 units [95% CI, 0.03 to 0.24] lower at the spine (p = 0.01) and 0.16 units [0.10 to 0.23] lower at the hip (\( p = {1} \times {1}{0^{ - {6}}} \)) than GG homozygotes. Clinical fractures were 1.31-fold [1.04–1.65] increased in TT homozygotes (p = 0.02) and vertebral fractures were 1.34-fold [1.01–1.77] increased (p = 0.04). We also observed associations between spine BMD and allelic variants at the -1997G/T (p = 0.05) and the -1663indelT (p = 0.009) sites. We found no association between alleles at the -1997G/T or -1663indelT sites and fracture but power was limited.

Conclusions

The COL1A1 Sp1 polymorphism is associated with a modest reduction in BMD and an increased risk of fracture, although we cannot fully exclude the possibility that the results may have been influenced by publication bias. Further studies are required to fully evaluate the contribution of the -1997G/T and -1663in/delT sites to these phenotypes and to determine if they interact with the Sp1 polymorphism to regulate susceptibility to osteoporosis.

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Title: Polymorphisms in the 5′ flank of COL1A1 gene and osteoporosis: meta-analysis of published studies
Authors: H. Jin
E. Evangelou
J. P. A. Ioannidis
S. H. Ralston
Publication date: 01-03-2011
Publisher: Springer-Verlag
Published in: Osteoporosis International / Issue 3/2011
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-010-1364-5

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Polymorphisms in the 5′ flank of COL1A1 gene and osteoporosis: meta-analysis of published studies

Abstract

Summary

Introduction and hypothesis

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Summary

Introduction and hypothesis

Methods

Results

Conclusions

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