Abstract

Genetic factors have been shown to have an important role in intervertebral disc disease. The associations of known genetic risk factors and whole-body vibration, a proposed environmental risk factor, for intervertebral disc disease (IDD) were evaluated. Eleven variations in eight genes (COL9A2, COL9A3, COL11A2, IL1A, IL1B, IL6, MMP-3 and VDR) were genotyped in 150 male train engineers with an average of 21-year exposure to whole-body vibration and 61 male paper mill workers with no occupational exposure to vibration. The number of individuals belonging to the IDD group was significantly higher among train engineers (42% of train engineers vs. 17.5% of sedentary workers; p = 0.005). In addition, the IL1A-889T allele represented a risk factor for the IDD-phenotype.

In order to clarify the role of genetic variations in the genes coding for several proinflammatory mediators, hundred fifty-five Finnish individuals with IDD were analyzed for mutations in the genes coding for inflammatory mediators IL-1α, IL-1β, IL-6 and TNF-α. In addition, sixteen single nucleotide polymorphisms (SNPs) in inflammatory mediator genes were genotyped. An association was identified between IDD and IL6 polymorphism +15T>A in exon 5 (p = 0.007). In addition, IL6 haplotype GGGA of -597G>A, -572G>C, -174G>C and +15T>A in exon 5 associated with IDD (p = 0.0033).

A functional SNP in the CILP gene has been suggested to cause IDD in the Japanese population. This functional variation was analyzed in 243 Finnish IDD patients and 259 controls, and in 348 Chinese individuals with degenerative MRI findings and 343 Chinese individuals with normal MRI. No association was found in the Finnish and Chinese study populations.

In order to reveal chromosomal susceptibility loci and new candidate gene(s) for IDD a genome-wide scan was performed on 14 Finnish families with 186 individuals. Genome-wide and fine mapping analysis provided maximum two-point LOD scores of 2.71, 2.36 and 2.04 for chromosomes 21, 4, and 6, respectively. Second fine mapping confirmed the susceptibility of chromosome 21. Two candidate genes, ADAMTS-1 and ADAMTS-5, were analyzed in the region suggesting linkage, leading to the identification of thirteen sequence variations. However, none of the variations were disease causing.