RESEARCH ARTICLE


An Association Study of Interleukin 18 Receptor Genes (IL18R1 and IL18RAP) in Lumbar Disc Degeneration



Ahmad Omair*, 1, Benedicte Alexandra Lie2, Olav Reikeras1, Jens Ivar Brox1
1 Department of Orthopaedics, Oslo University Hospital-Rikshospitalet, Oslo, Norway
2 Department of Immunology, Oslo University Hospital-Rikshospitalet, Oslo, Norway


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Creative Commons License
© Omair et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Department of Orthopaedics, Oslo University Hospital-Rikshospitalet, Sognsvannsveien 20, 0027 Oslo, Norway; Tel: +47-93687989, +47-23076053; Fax: +47-23076010; E-mail: ahmad.omair@ous-hf.no


Abstract

Objectives:

To examine association of candidate genetic variants in structural, inflammatory, matrix modifying, vitamin D receptor genes and variants associated with osteoarthritis, with surgical candidates and surgical patients with lumbar disc degeneration (LDD), in light of their previously reported susceptibility for LDD.

Methods:

Genotyping of 146 Norwegian LDD patients and 188 Norwegian controls was performed for 20 single-nucleotide polymorphisms (SNPs) from collagen, aggrecan, interleukin, VDR, MMP3 and COX2 genes and 7 SNPs from osteoarthritic genes.

Results:

The neighboring genes IL18R1 and IL18RAP polymorphisms (rs2287037 and rs1420100), showed a statistically non-significant risk for developing LDD (OR 1.36 [95 % CI 0.99 – 1.87]; p=0.06 and OR 1.33 [95 % CI 0.98-1.81]; p=0.07). Homozygosity of these risk alleles was associated with LDD (p=0.023 and p=0.027). The non-risk alleles at these SNPs were situated on a haplotype negatively associated with LDD (p=0.008). Carriage of at least one non-risk allele at both loci also reduces the risk of developing LDD (OR 0.51 [95 % CI 0.33-0.80]; p=0.003).

Conclusion:

Our findings support the polygenic nature of LDD and suggest that variation in interleukin 18 receptor genes could affect the risk of severe LDD and associated low back pain.

Keywords: Candidate genes, interleukin 18 receptor 1, interleukin 18 receptor accessory protein, low back pain, lumbar disc degeneration, Single-nucleotide polymorphisms.