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1.  Modic changes and interleukin 1 gene locus polymorphisms in occupational cohort of middle-aged men 
European Spine Journal  2009;18(12):1963-1970.
According to recent systematic reviews, Modic changes are associated with low-back pain. However, their pathophysiology remains largely unknown. A previous study of Northern Finnish males implicated that IL1A and MMP3 polymorphisms play a role in type II Modic changes. The purpose of the current study was to examine the association of IL1 cluster polymorphisms with Modic changes amongst middle-aged men in Southern Finland. The final study sample consisted of 108 men from three different occupations, who underwent magnetic resonance imaging (MRI) with a 0.1 T-scanner. Six single nucleotide polymorphisms (SNP) in the IL1 gene cluster (IL1A c.1-889C>T; IL1B c.3954C>T; IL1RN c.1812G>A; IL1RN c.1887G>C; IL1RN c.11100T>C; IL1RN c.1506G>A) were genotyped with the SNP-TRAP method or by allele-specific primer extension on modified microarray. In all, 45 subjects had Modic changes at one or more disc levels. The presence of the minor allele of IL1A (c.1-889C>T) was associated with these changes (any Modic change p = 0.031, type II changes p = 0.036). The carriers of the T-allele had a 2.5-fold risk of Modic change and the association was independent of the other IL1 gene cluster loci studied. In addition, a minor haplotype, with a frequency of 7.5% in the study population, including the minor alleles of IL1A c.1-889C>T, IL1RN c.1812G>A, and IL1RN c.1506G>A, was significantly associated with Modic changes. This observation is in accordance with the previous finding from a different geographical area, and thus confirms the importance of the IL1A gene in the pathophysiology of Modic changes.
doi:10.1007/s00586-009-1139-x
PMCID: PMC2899448  PMID: 19701653
Modic changes; MRI; Genetic factors; Interleukin
2.  Effectiveness of early part-time sick leave in musculoskeletal disorders 
Background
The importance of staying active instead of bed rest has been acknowledged in the management of musculoskeletal disorders (MSDs). This emphasizes the potential benefits of adjusting work to fit the employee's remaining work ability. Despite part-time sick leave being an official option in many countries, its effectiveness has not been studied yet. We have designed a randomized controlled study to assess the health effects of early part-time sick leave compared to conventional full-day sick leave. Our hypothesis is that if work time is temporarily reduced and work load adjusted at the early stages of disability, employees with MSDs will have less disability days and faster return to regular work duties than employees on a conventional sick leave.
Methods/Design
The study population will consist of 600 employees, who seek medical advice from an occupational physician due to musculoskeletal pain. The inclusion requires that they have not been on a sick leave for longer than 14 days prior to the visit. Based on the physician's judgement, the severity of the symptoms must indicate a need for conventional sick leave, but the employee is considered to be able to work part-time without any additional risk. Half of the employees are randomly allocated to part-time sick leave group and their work time is reduced by 40–60%, whereas in the control group work load is totally eliminated with conventional sick leave. The main outcomes are the number of days from the initial visit to return to regular work activities, and the total number of sick leave days during 12 and 24 months of follow-up. The costs and benefits as well as the feasibility of early part-time sick leave will also be evaluated.
Conclusion
This is the first randomised trial to our knowledge on the effectiveness of early part-time sick leave compared to conventional full-time sick leave in the management of MSDs. The data collection continues until 2011, but preliminary results on the feasibility of part-time sick leave will be available already in 2008. The increased knowledge will assist in better decision making process regarding the management of disability related to MSDs.
Trial Registration
International Standard Randomised Controlled Trial Number Register, register number ISRCTN30911719
doi:10.1186/1471-2474-9-23
PMCID: PMC2267790  PMID: 18294405
3.  Common interleukin-6 promoter variants associate with the more severe forms of distal interphalangeal osteoarthritis 
Introduction
The objective of this study was to investigate the relationship of the IL-6 promoter variants G-597A, G-572C and G-174C (rs1800797, rs1800796 and rs1800795, respectively), which have been shown to affect both the transcription and secretion of IL-6, to symptomatic distal interphalangeal (DIP) osteoarthritis (OA).
Methods
A total of 535 women aged 45 to 63 years were included. Radiographs of both hands were taken and each DIP joint was evaluated (grade 0 to 4) for the presence of OA. Information on symptoms (pain, tenderness) in each joint was collected by using a self-administered questionnaire. Symptomatic DIP OA was defined by the presence of both radiographic findings of grade 2 or more and symptoms in at least two DIP joints, and symmetrical DIP OA by the presence of radiographic findings of grade 2 or more in at least one symmetrical pair of DIP joints. Common polymorphic loci in the IL-6 gene were amplified and the promoter haplotypes were reconstructed from genotype data with the PHASE program. Logistic regression analysis was used to examine the association between the IL-6 genotypes/diplotypes and the DIP OA outcome.
Results
The G alleles of two promoter single nucleotide polymorphisms (SNPs) G-597A and G-174C were more common among the subjects with symptomatic DIP OA than among those with no disease (P = 0.020 and 0.024, corrected for multiple testing). In addition, the carriage of at least one G allele in these positions increased the risk of disease (P = 0.006 and P = 0.008, respectively). Carrying a haplotype with the G allele in all three promoter SNPs increased the risk of symptomatic DIP OA more than fourfold (odds ratio (OR) 4.45, P = 0.001). Carriage of the G-G diplotype indicated an increased risk of both symmetrical DIP OA (OR 1.52, 95% confidence interval 1.01 to 2.28) and symptomatic DIP OA (OR 3.67, 95% confidence interval 1.50 to 9.00).
Conclusion
The present study showed that the presence of G alleles at common IL-6 polymorphic promoter loci was associated with the more severe DIP OA outcomes, symmetrical and symptomatic.
doi:10.1186/ar2374
PMCID: PMC2374458  PMID: 18257935
4.  Intervertebral disc degeneration in relation to the COL9A3 and the IL-1ß gene polymorphisms 
European Spine Journal  2005;15(5):613-619.
Disc degeneration is a complex condition in which environmental factors and multiple genes are expected to act together to determine the degenerative phenotype. Recently associations of COL9A2 (Trp2 allele) and COL9A3 (Trp3 allele) polymorphisms with lumbar disc disease characterized by sciatica have been reported. However, it is not known whether the Trp2 or Trp3 alleles contribute to disc degeneration (DD). In this study, the association between the collagen genes polymorphisms and lumbar DD was investigated. Furthermore, the influence of the IL-1β(C3954-T) polymorphism on the association of collagen genes polymorphisms with DD was examined. Lumbar intervertebral discs of 135 middle-aged occupationally active men were evaluated with magnetic resonance imaging, using decreased signal intensity of the nucleus pulposus, disc bulges, and decreased disc height as signs of degeneration. Blood samples were analysed for the presence of COL9A3 and COL9A2 tryptophan alleles (Trp3 and Trp2 alleles). The COL11A2, COL2A1 and IL-1β(C3954-T) polymorphisms were also analysed. Multivariate logistic regression analysis allowing for occupation and body mass index showed that the carriage of the Trp3 allele in the absence of the IL-1βT3954 allele increased the risk of dark nucleus pulposus (OR 7.0, 95% CI 1.3–38.8) and joint occurrence of degenerative changes (OR 8.0, 95% CI 1.4–44.7). There was no effect of the Trp3 allele on DD in the presence of the IL-1βT3954 allele. The carriers of the COL11A2 minor allele had an increased risk of disc bulges (OR 2.1, 95% CI 1.0–4.2) as compared with non-carriers. The results suggest that the effect of the COL9A3 gene polymorphism on DD might be modified by the IL-1β gene polymorphism.
doi:10.1007/s00586-005-0988-1
PMCID: PMC3489335  PMID: 16133074
Lumbar disc degeneration; Magnetic resonance imaging; COL9A3; IL-1β
5.  Vitamin D receptor gene polymorphisms and susceptibility of hand osteoarthritis in Finnish women 
We examined whether polymorphisms of the vitamin D receptor (VDR) gene was associated with individual risk of hand osteoarthritis (OA). Radiographs of both hands of 295 dentists and of 248 teachers were examined and classified for the presence of OA using reference images. The VDR ApaI and TaqI genotypes were determined by PCR-based methods. No association was observed between the VDR polymorphisms and the odds of overall hand OA. However, the carriers of the VDR t allele or At haplotype were at almost half the odds of symmetrical hand OA (odds ratio [OR] = 0.60, 95% confidence interval [CI] = 0.38–0.94 and OR = 0.59, 95% CI = 0.38–0.93, respectively) compared with the carriers of the T allele and of the non-At haplotype, respectively. Increased odds of this disease, on the contrary, was observed for women with two copies of the VDR a allele (OR = 1.93, 95% CI = 1.99–3.70) compared with women with the AA genotype. Conversely, the VDR a allele carriage was associated with a tendency of lowered odds of osteophyte (OR = 0.51, 95% CI = 0.25–1.03). When the genotype data were used to construct haplotypes, the VDR AaTt joint genotype appeared to pose a remarkably lower odds (OR = 0.26, 95% CI = 0.08–0.91) of osteophyte compared with the AAtt joint genotype. As a novel finding we observed a joint effect of a low calcium intake and VDR polymorphisms on symmetrical OA; the OR was 2.64 (95% CI = 1.29–5.40) for carriers of the aT haplotype with low daily calcium intake compared with non-carriers of the haplotype with high daily calcium intake. Our results suggest that VDR gene polymorphisms play a role in the etiology of symmetrical hand OA. Moreover, the association between the VDR gene and OA may be modified by calcium intake.
doi:10.1186/ar1874
PMCID: PMC1526549  PMID: 16507122
6.  Work stress and risk of cardiovascular mortality: prospective cohort study of industrial employees 
BMJ : British Medical Journal  2002;325(7369):857.
Objective
To examine the association between work stress, according to the job strain model and the effort-reward imbalance model, and the risk of death from cardiovascular disease.
Design
Prospective cohort study. Baseline examination in 1973 determined cases of cardiovascular disease, behavioural and biological risks, and stressful characteristics of work. Biological risks were measured at 5 year and 10 year follow up.
Setting
Staff of a company in the metal industry in Finland.
Participants
812 employees (545 men, 267 women) who were free from cardiovascular diseases at baseline.
Main outcome measure
Cardiovascular mortality 1973-2001 from the national mortality register.
Results
Mean length of follow up was 25.6 years. After adjustment for age and sex, employees with high job strain, a combination of high demands at work and low job control, had a 2.2-fold (95% confidence interval 1.2 to 4.2) cardiovascular mortality risk compared with their colleagues with low job strain. The corresponding risk ratio for employees with effort-reward imbalance (low salary, lack of social approval, and few career opportunities relative to efforts required at work) was 2.4 (1.3 to 4.4). These ratios remained significant after additional adjustment for occupational group and biological and behavioural risks at baseline. High job strain was associated with increased serum total cholesterol at the 5 year follow up. Effort-reward imbalance predicted increased body mass index at the 10 year follow up.
Conclusions
High job strain and effort-reward imbalance seem to increase the risk of cardiovascular mortality. The evidence from industrial employees suggests that attention should be paid to the prevention of work stress.
What is already known on this topicJob strain (high demands and low job control) and effort-reward imbalance (high demands, low security, few career opportunities) elicit stress at workTheir status as risk factors for cardiovascular mortality has, however, remained uncertainWhat this study addsJob strain and effort-reward imbalance were each associated with a doubling of the risk of cardiovascular death among employees who were free from overt cardiovascular diseases at baselineJob strain and effort-reward imbalance also predicted adverse changes in biological factors such as cholesterol concentration and body mass index
PMCID: PMC129630  PMID: 12386034

Results 1-6 (6)