Allelic variants of IL1R1 gene associate with severe hand osteoarthritis

BACKGROUND: In search for genes predisposing to osteoarthritis (OA), several genome wide scans have provided evidence for linkage on 2q. In this study we targeted a 470 kb region on 2q11.2 presenting the locus with most evidence for linkage to severe OA of distal interphalangeal joints (DIP) in our genome wide scan families. METHODS: We genotyped 32 single nucleotide polymorphisms (SNPs) in this 470 kb region comprising six genes belonging to the interleukin 1 superfamily and monitored for association with individual SNPs and SNP haplotypes among severe familial hand OA cases (material extended from our previous linkage study; n = 134), unrelated end-stage bilateral primary knee OA cases (n = 113), and population based controls (n = 436). RESULTS: Four SNPs in the IL1R1 gene, mapping to a 125 kb LD block, provided evidence for association with hand OA in family-based and case-control analysis, the strongest association being with SNP rs2287047 (p-value = 0.0009). CONCLUSIONS: This study demonstrates an association between severe hand OA and IL1R1 gene. This gene represents a highly relevant biological candidate since it encodes protein that is a known modulator of inflammatory processes associated with joint destruction and resides within a locus providing consistent evidence for linkage to hand OA. As the observed association did not fully explain the linkage obtained in the previous study, it is plausible that also other variants in this genome region predispose to hand OA.Peer reviewe

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

The Role of back injury or trauma in lumbar disc degeneration : an exposure-discordant twin study

Study Design. Exposure discordant twin study. Objective. To investigate the effect of injury on lumbar disc degeneration in monozygotic twins with discordant exposures to recalled previous injury/trauma to the lumbar spine. Summary of Backgrounf Data. Disc degeneration is considered a primary source of low back pain. Despite this, important determinants of disc degeneration other than genotype have not been identified. One possible important determinant of disc degeneration that has undergone limited investigation is previous back injury. Methods. We compared disc degeneration between 37 male monozygotic twin pairs with discordant exposures to recalled previous injury/trauma to the lumbar spine. Data on injury history were obtained through an extensive structured interview. Disc degeneration was assessed using quantitative measures of disc height and disc signal intensity. Results. Disc degeneration did not differ between twins who reported previous back injury and their uninjured cotwins. This finding was consistent for both disc height and disc signal intensity regardless of whether mean scores or greatest difference at any one lumbar level was used in the analysis. Disc height averaged 0.3 mm higher in the injured twin (P = 0.302), and was on average 0.05% higher at the level of the greatest cotwin difference (P = 0.302). There was no evidence that greater period since injury resulted in greater twin differences in disc degeneration. Conclusion. The current study suggests that back injury based on patient report is not an important predictor of future disc degeneration.5 page(s

Heritability of lumbar flexibility and the role of disc degeneration and body weight

Spinal range of motion is evaluated in assessing patients with back problems and monitoring outcomes, as well as in general fitness assessments. Yet, determinants of the substantial interindividual variation in spinal range of motion are not well understood. Substantial genetic effects on global measures of range of motion and hypermobility have been suggested from earlier studies, but genetic influences specifically on spinal range of motion have not been previously studied. The objectives of the present study were to investigate the relative role of genetic and environmental influences on lumbar range of motion in adult men and the pathways through which genes may influence range of motion. Thus we conducted a classic twin study of 300 monozygotic and dizygotic male twin pairs with consideration of covariates, using standard statistical methods. All subjects underwent a clinical examination, including general anthropometrics, lumbar range of motion, and lumbar MRI to assess disc degeneration, as well as an extensive interview on environmental and behavioral exposures and back pain history. We found the proportion of variance in lumbar range of motion attributable to genetic influences (heritability estimate) to be 47%. The extent of lumbar range of motion in flexion was predominantly determined by genetic influences (64%), while extension was influenced to a somewhat greater degree by environmental and behavioral factors. Statistically significant age-adjusted genetic correlations were found between lumbar extension and disc degeneration variables (ra = –0.38 to –0.43) and between flexion and body weight (ra = –0.33), suggesting two pathways through which genes influence lumbar range of motio

Lumbar Disc Degeneration and Sagittal Flexibility

Summary: It is uncertain whether intervertebral disc degeneration is associated with reduced or increased flexibility, although lumbar flexibility is known to reduce with advancing age. This cross-sectional study of 214 middle-aged men attempted to determine the influence on lumbar sagittal flexibility from intervertebral disc degeneration parameters measured from magnetic resonance images (disc height, signal intensity, bulging, osteophytes). Multivariate analyses showed that a reduced extent of lumbar flexibility could be accounted for by the combined effect of decreasing disc height together with increasing age, weight, and back pain frequency. Although it remains possible that single degenerate discs will display increased mobility, the presence of discs at various stages of degeneration results in a net reduction of flexibility. The factors studied here explained only 31% of the variance in flexibility; the major determinants remain to be identified and quantified