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Int J Mol Epidemiol Genet 2012;3(3):195-204

Original Article
Gender difference in genetic association between IL1A variant and early
lumbar disc degeneration: a three-year follow-up

Pasi J Eskola, Per Kjaer, Joan S Sorensen, Annaleena Okuloff, Niels Wedderkopp, Iita Daavittila, Leena Ala-Kokko, Minna
Männikkö, Jaro Karppinen

Oulu Center for Cell – Matrix Research, Biocenter and Department of Medical Biochemistry and Molecular Biology, University of
Oulu, Oulu, Finland; Institute of Sports Science and Clinical Biomechanics, University of Southern Denmark, Clinical
Locomotion Network, Odense, Denmark; Research Department, Spine Centre of Southern Denmark, Hospital Lillebaelt,
Institute of Regional Health Services Research, Clinical Locomotion Network, University of Southern Denmark, Middelfart,
Denmark; Wilhelm Johannsen Centre For Functional Genome Research, Department of Cellular and Molecular Medicine,
University of Copenhagen, Denmark; Finnish Institute of Occupational Health, Health and Work Ability, and Disability Prevention
Centre, Oulu, Finland; Connective Tissue Gene Tests, Allentown, USA; Institute of Clinical Medicine, Department of Physical
and Rehabilitation Medicine, University of Oulu, PL 5000, 90014 Oulu, Finland

Received June 26, 2012; accepted August 5, 2012; Epub August 31, 2012; Published September 15, 2012

Abstract: Objective: The purpose of the present study was to analyze the associations between specific genetic markers and
early disc degeneration (DD) or early disc degeneration progression (DDP) defined by magnetic resonance imaging (MRI).
Methods: We selected eleven of the most promising single nucleotide polymorphisms (SNP) and compared the distributions of
these genetic markers between groups defined by MRI in a Danish adolescent population (N=166) over a three-year follow-up
period. Results: We observed a ten-fold higher annual incidence of endplate changes than previously reported in adults. The
gender difference in IL1A rs1800587 association with DD remained significant and another association with DDP emerged in
follow-up assessment. Among girls, the rs1800587 T-allele was associated both with DD (OR 2.82 [95% CI 1.29–6.16]) and
with DDP (OR 2.45 [95% CI 1.03–5.82]). Among boys, the IL6 rs1800795 genotype G/C was protective in both DD (OR 0.26
[95% CI 0.09–0.72]) and DDP (OR 0.32 [95% CI 0.12–0.88]) with the IL6 rs1800797 genotype G/A was associated with a
decreased likelihood of DD (OR 0.27 [95% CI 0.10–0.77]). Gender-genotype interactions were significant for polymorphisms in
both IL1A and IL6. Correction for multiple testing weakened the associations for IL6 polymorphisms. Conclusion: We conclude
that gender specific effects in lumbar disc degeneration and its progression are possible. However, further evaluations in
larger populations are needed. Our results provide some support to the hypothesis that early disc degeneration is an
especially important phase in the cascade of degenerative disc disease. (IJMEG1206002).

Keywords: Disc degeneration, disc degeneration progression, adolescents, genetics, interleukins


Address all correspondence to:
Dr. Jaro Karppinen, Finnish Institute of Occupational Health, Health and Work Ability, and Disability Prevention Centre, Oulu,
Finland; Institute of Clinical Medicine, Department of Physical and Rehabilitation Medicine, University of Oulu, PL 5000, 90014
Oulu, Finland Tel: +358414462859; Fax: +35883153501; E-mail: jaro.karppinen@ttl.fi