title: Genetic variations in IL6 associate with intervertebral disc disease characterized by sciatica.
abstract: 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.
authors.affiliation: Collagen Research Unit, Biocenter and Department of Medical Biochemistry and Molecular Biology, University of Oulu, Aapistie 5A, 90220 Oulu, Finland.
authors.forename: Noora
authors.initials: N
authors.lastname: Noponen-Hietala
authors.forename: Iita
authors.initials: I
authors.lastname: Virtanen
authors.forename: Riitta
authors.initials: R
authors.lastname: Karttunen
authors.forename: Susanne
authors.initials: S
authors.lastname: Schwenke
authors.forename: Eveliina
authors.initials: E
authors.lastname: Jakkula
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Riitta
authors.initials: R
authors.lastname: Merikivi
authors.forename: Sandra
authors.initials: S
authors.lastname: Barral
authors.forename: Jürg
authors.initials: J
authors.lastname: Ott
authors.forename: Jaro
authors.initials: J
authors.lastname: Karppinen
authors.forename: Leena
authors.initials: L
authors.lastname: Ala-Kokko
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D007405:Intervertebral Disc Displacement / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D012585:Sciatica / Q000235:genetics*
chemical_list: D015850:Interleukin-6