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Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_9 | Pages 24 - 24
1 Sep 2019
Freidin M Kraatari M Skarp S Määttä J Kettunen J Niinimäki J Karppinen J Männikkö M Williams F
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Objective

Modic changes (MC), a form of intervertebral disc degeneration visible as subchondral and vertebral bone marrow changes on spine magnetic resonance (MR), are known to be associated with low back pain. This study aimed to identify genes contributing to the development of MC using genome-wide association study.

Methods

Presence of MC was evaluated in lumbar MR images in the Northern Finland Birth Cohort 1966 (NFBC1966, N=1182) and TwinsUK (N=647). Genome-wide association analyses were carried out in the cohorts separately using a linear regression model fitted to test for additive effects of SNPs and adjusting for age, sex, BMI, and either family relatedness via a kinship matrix (TwinsUK) or population stratification using principal components (NFBC1966). Meta-analysis of the two studies was carried out using the inverse-variance weighting approach.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 278 - 278
1 May 2009
Daavittila I Solovieva S Kuisma M Taimela S Natri A Korpelainen R Niinimäki J Tervonen O Ala-Kokko L Männikkö M Karppinen J
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Introduction: Modic changes are vertebral endplate changes visible in magnetic resonance imaging (MRI), which associate with degenerative intervertebral disc disease. Twin studies suggest that intervertebral disc degeneration and low back pain may be primarily explained by genetic factors. There are, however, no studies on genetic factors in Modic changes.

Materials and methods: Eleven variations in eight genes (COL9A2, COL9A3, COL11A2, IL1A, IL1B, IL6, MMP-3 and VDR) were genotyped in an occupational cohort of 159 male train engineers and 69 male paper mill workers. All the study subjects were MRI scanned and evaluated for Modic changes.

Results: Out of 228 subjects studied, 128 (56%) were found to have Modic change at one or more disc levels. 15% of them had exclusively Modic type I while 32% had exclusively Modic II changes. 10% of the subjects had both type I and type II changes. When single nucleotide polymorphisms (SNPs) were analyzed independently, none of them significantly associated with Modic changes. However, when the gene-gene interactions were evaluated IL1A and MMP-3 polymorphisms together associated with type II Modic changes (OR 3.2, 95% CI 1.2–8.5; p = 0.038). Furthermore, IL-1 gene cluster together with MMP-3 polymorphism associated significantly with type II Modic changes (OR = 8.14, 95% CI 1.72–38.44; p = 0.008).

Discussion: This is the first study evaluating the role of genetic factors in relation to Modic changes. Genetic variations in IL-1 cluster and MMP-3 gene were found together to associate significantly with type II Modic changes.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 282 - 282
1 May 2009
Karppinen J Daavittila I Noponen N Männikkö M Haapea M Taimela S Vanharanta H Ala-Kokko L
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Introduction: We have shown that an IL6 haplotype (GGGA) associates with intervertebral disc disease (IDD) characterized by sciatica. However, its prognostic value for IDD is not known.

Materials and methods: DNA from 153 sciatica patients, who participated in a randomized controlled trial of periradicular infiltration, was analyzed for IL6 variations: c.1–597G> A, c.1–572G> C, c.1–174G> C, and c.486T> A (Genebank #NM_000600.1). Patients recorded back and leg pain intensity and duration (number of days with pain), Oswestry disability, and back-related sick leaves. Repeated measures ANCOVA with adjustment for age, gender and physical work load was used. Square root transformations of outcome data at one, two and three years after the intervention were used for skewed variables.

Results: The prevalence of the GGGA haplotype was 9% (14/153). Data was available from 10 (sick leaves) to 13 (VAS) subjects with and from 107 to 124 subjects without the haplotype. The groups did not differ with respect to pain intensities, or disability. Days with back and leg pain and sick leaves were significantly higher among subjects with the IL6 haplotype (p=0.024, 0.002 and 0.022, respectively). An interaction of the IL6 haplotype and physical work load was significant for duration of back and leg pain and sick leaves (p=0.010, 0.004 and 0.018, respectively).

Discussion: This is the first observation of any prognostic genotype among sciatica patients. The IL6 haplotype GGGA predicted the number of days with back or leg pain, and sickness absence. Subjects with the IL6 haplotype may be more vulnerable when exposed to physically demanding job.