Genetic Influences on Hand Osteoarthritis in Finnish Women - A Replication Study of Candidate Genes

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Association study of MMP8 gene in osteoarthritis

Objectives: Osteoarthritis (OA) is a joint disease common in the elderly. There is a prior functional evidence for different matrix metalloproteinases (MMPs), such as MMP8 and MMP9, having a role in the breakdown of cartilage extracellular matrix in OA. Thus, we analyzed whether the common genetic variants of MMP8 and MMP9 contribute to the risk of OA. Materials and methods: In total, 13 common tagging single-nucleotide polymorphisms (SNPs) were studied in a discovery knee OA cohort of 185 cases and 895 controls. For validation, two knee OA replication cohorts and two hand OA replication cohorts were studied (altogether 1369 OA cases, 4445 controls in the five cohorts). The chi(2) test for individual study cohorts and Cochran-Mantel-Haenszel test for combined meta-analysis were calculated using Plink. Results: The rs1940475 SNP in MMP8 showed suggestive association in the discovery cohort (OR = 0.721, 95% CI 0.575-0.906; p = 0.005). Other knee and hand OA replication study cohorts showed similar trend for the predisposing allele without reaching statistical significance in independent replication cohorts nor in their meta-analysis (p > 0.05). Meta-analysis of all five hand and knee OA study cohorts yielded a p-value of 0.027 (OR = 0.904, 95% CI 0.826-0.989). Conclusions: Initial analysis of the MMP8 gene showed suggestive association between rs1940475 and knee OA, but the finding did not replicate in other study cohorts, even though the trend for predisposing allele was similar in all five cohorts. MMP-8 is a good biological candidate for OA, but our study did not find common variants with significant association in the gene.Peer reviewe

Trajectories of a set of ten functional somatic symptoms from adolescence to middle age

Background: Functional somatic symptoms (FSS), or symptoms without a clear medical explanation are a considerable challenge for health care systems. There is no general consensus as to which symptoms should be regarded functional. Few longitudinal studies on the development of FSS exist and these have mainly been based on the assumption that the factorial structure of a FSS scores variable remains invariant over time. When the analysis covers longer periods of the life course, this may be challenged. The aim of our study was to investigate how ten functional somatic symptoms (FSS) evolve when individuals are ageing. Methods: The data of the Northern Swedish Cohort (n = 1001) from questionnaire surveys at ages 16, 18, 21, 30 and 42, were analysed. Participation rates remained very high over the five surveys. The list of symptoms included backache, breathlessness, dizziness, fatigue, headache or migraine, nausea, overstrain, palpitations, sleeplessness and stomach ache. We used multivariate trajectory analysis (TA) with logistic broken-stick regression models to describe sub-groups in the data. In multivariate TA the joint development of the set of item variables can be investigated. There is no need to construct a special FSS summary score variable. Results: Four well separated trajectories were identified. In two groups, healing symptoms (25.4% of the sample) and low symptom load (32.2% of the sample), the symptom level stayed relatively low in adulthood. In the third group of high symptom load (17.2%) the probability of having symptoms was high for all FSS variables. In the fourth group of increasing symptoms (25.3%) the level of symptoms was first intermediate, but increased markedly with age. Conclusions: Instead of a single FSS score we were able to assign each individual to one of four trajectories described jointly by 10 separate symptoms. The profile of development, but not the probability level, was rather similar over the symptoms within the trajectories, with few exceptions. The results provide better understanding of the longitudinal development of the symptoms from the adolescence to the middle age

Work-family conflicts and long-term medically certified sickness absence due to mental disorders - a follow-up study of female municipal employees

Background. Decreased work ability due to mental disorders is a growing concern in Europe. We studied the role of work-family conflicts in association with long-term sickness absence due to mental disorders (LTSA-MD).Methods. Baseline data were extracted from the Helsinki Health Study for women aged 40 to 55 in full-time work in 2001 - 2002 (N = 2386). Questionnaire responses were linked with register data from the Social Insurance Institution of Finland on SA spells due to mental disorders during 2004-2010. We studied an overall question on satisfaction with combining work and family (WFS) and composite scores of work-to-family conflicts (WTFC) and family-to-work-conflicts (FTWC), and their components in association with the first certified SA spell (>= 12 calendar days) due to a mental disorder during the follow-up. We performed Cox regression analyses with hazard ratios (HR) and their 95% confidence intervals (CI) adjusted for sociodemographic factors, work schedule, perceived mental and physical strenuousness at work, and self-rated health. First, we examined all participants, and second, only those who reported no prior mental disorder.Results. Poor work-family satisfaction (WFS) was associated with subsequent LTSA-MD, adjusting for all covariates (HR 1.60; 95% CI 1.10-2.16). Both high WTFC (1.64; 1.15-2.23), and high FTWC (1.43; 1.02-2.00) increased the probability of LTSA-MD in the full model. When participants with prior mental disorder were excluded, the association between poor WFS and WTFC with LTSA-MD retained while that between FTWC and LTSA-MD attenuated; however, two items of the FTWC were still associated with LTSA-MD: 'Family worries and problems distract you from your work' and 'Family matters prevent you from sleeping enough to do your job well'. Of the WTFC items, the following remained associated with LTSA-MD: 'Problems at work make you irritable at home' and 'Your job takes so much energy you do not feel up to doing things that need attention at home'. The experience of decreased time for work or family did not associate with LTSA-MD.Conclusions. Among female municipal employees, dissatisfaction with combining work and family and both work-to-family and family-to-work conflicts were associated with subsequent long-term sickness absence due to mental disorders.Peer reviewe