Genetic variations in IL6 associate with intervertebral disc disease characterized by sciatica

Intervertebral disc disease (IDD) characterized by sciatica is a common disorder affecting about 5% of individuals. Environmental factors can predispose to this disease, but IDD has a strong genetic background. Recent evidence suggests that inflammation is one of the key factors in the etiology of IDD. Here, a possible role of the inflammatory mediator genes was studied in 155 patients with IDD-related sciatica and 179 controls. Forty-eight patients were analyzed for mutations in the IL1A, IL1B, IL6 and TNFA genes, and 16 polymorphisms in 10 candidate cytokine genes ( IL1A, IL1B, IL1RN, TNFA, IL2, IL4, IL4R, IL6, IL10, IFNG) were genotyped from all subjects. No disease-causing mutations were identified in IL1A, IL1B, IL6 or TNFA. Allele frequencies were, however, significantly different between the two groups for IL6 SNP, T15A in exon 5 ( P=0.007). Furthermore, the genotypes AA and AT of the exon 5 SNP were more common in the patients ( P=0.011; OR=4.4, 95% CI=1.2–15.7; AR=7.5%, 1.6–13.1%). Haplotypes were then generated for four IL6 SNPs, G-597A, G-572C, G-174C, and T15A in exon 5. Haplotype GGGA was more common in the patients ( P=0.011; OR=4.8, 95% CI=1.6–14.5). To evaluate attributable risk, haplotype pairs were assigned for the individuals. The presence of GGGA/GGGA or GGGA/other genotypes had an OR of 5.4 (95% CI=1.5–19.2). Association of GGGA with disease was highly significant ( P=0.0033), and the associated AR was 6.8% (1.9–11.5%). These findings support the role of IL-6 genetic variations in discogenic pain.