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

ABSTRACT: 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.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.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.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 x 10??) 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.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.

SUBMITTER: Jin H

PROVIDER: S-EPMC4696542 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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

Jin H H Evangelou E E Ioannidis J P A JP Ralston S H SH

Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 20100827 3

<h4>Unlabelled</h4>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.<h4>Introduction and hypothesis</h4>Polymorphisms in the 5' flank of COL1A1 gene have been implicated as genetic markers for susce ...[more]

PMID: 20798928

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Project description:ObjectiveTo systematically review published and unpublished efficacy studies of agomelatine in people with depression.DesignSystematic review and meta-analysis.Data sourcesLiterature search (Pubmed, Embase, Medline), Cochrane Central Register of Controlled Trials, European Medicines Agency (EMA) regulatory file for agomelatine, manufacturers of agomelatine (Servier).Eligibility criteriaDouble blind randomised placebo and comparator controlled trials of agomelatine in depression with standard depression rating scales.Data synthesisStudies were pooled by using a random effects model with DerSimonian and Laird weights for comparisons with placebo and comparator antidepressant. The primary efficacy measure (change in rating scale score) was summarised with standardised mean difference (SMD; a measure of effect size) and secondary outcome measures with relative risks. All results were presented with 95% confidence intervals. Statistical heterogeneity was explored by visual inspection of funnel plots and by the I(2) statistic. Moderators of effect were explored by meta-regression.ResultsWe identified 20 trials with 7460 participants meeting inclusion criteria (11 in the published literature, four from the European Medicines Agency file, and five from the manufacturer). Almost all studies used the 17 item Hamilton depression rating scale (score 0-50). Agomelatine was significantly more effective than placebo with an effect size (SMD) of 0.24 (95% confidence interval 0.12 to 0.35) and relative risk of response 1.25 (1.11 to 1.4). Compared with other antidepressants, agomelatine showed equal efficacy (SMD 0.00, -0.09 to 0.10). Significant heterogeneity was uncovered in most analyses, though risk of bias was low. Published studies were more likely than unpublished studies to have results that suggested advantages for agomelatine.ConclusionsAgomelatine is an effective antidepressant with similar efficacy to standard antidepressants. Published trials generally had more favourable results than unpublished studies.

Project description:It has been proposed that night shift work could increase breast cancer incidence. A 2007 World Health Organization review concluded, mainly from animal evidence, that shift work involving circadian disruption is probably carcinogenic to humans. We therefore aimed to generate prospective epidemiological evidence on night shift work and breast cancer incidence.Overall, 522 246 Million Women Study, 22 559 EPIC-Oxford, and 251 045 UK Biobank participants answered questions on shift work and were followed for incident cancer. Cox regression yielded multivariable-adjusted breast cancer incidence rate ratios (RRs) and 95% confidence intervals (CIs) for night shift work vs no night shift work, and likelihood ratio tests for interaction were used to assess heterogeneity. Our meta-analyses combined these and relative risks from the seven previously published prospective studies (1.4 million women in total), using inverse-variance weighted averages of the study-specific log RRs.In the Million Women Study, EPIC-Oxford, and UK Biobank, respectively, 673, 28, and 67 women who reported night shift work developed breast cancer, and the RRs for any vs no night shift work were 1.00 (95% CI?=?0.92 to 1.08), 1.07 (95% CI?=?0.71 to 1.62), and 0.78 (95% CI?=?0.61 to 1.00). In the Million Women Study, the RR for 20 or more years of night shift work was 1.00 (95% CI?=?0.81 to 1.23), with no statistically significant heterogeneity by sleep patterns or breast cancer risk factors. Our meta-analysis of all 10 prospective studies included 4660 breast cancers in women reporting night shift work; compared with other women, the combined relative risks were 0.99 (95% CI?=?0.95 to 1.03) for any night shift work, 1.01 (95% CI?=?0.93 to 1.10) for 20 or more years of night shift work, and 1.00 (95% CI?=?0.87 to 1.14) for 30 or more years.The totality of the prospective evidence shows that night shift work, including long-term shift work, has little or no effect on breast cancer incidence.

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

Publications

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

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