Association between IL-6 and MMP-3 gene polymorphisms and adolescent idiopathic scoliosis : A case-control study

• Published in: Spine (Philadelphia, Pa. 1976) Pa. 1976), 2007-11, Vol.32 (24), p.2700-2702
• Main Authors: AULISA, Lorenzo, PAPALEO, Pierangelo, POLA, Enrico, ANGELINI, Flavia, AULISA, Angelo G, TAMBURRELLI, Francesco C, POLA, Paolo, LOGROSCINO, Carlo A
• Format: Article
• Language: English
• Subjects: Adolescent; Biological and medical sciences; Case-Control Studies; Cerebrospinal fluid. Meninges. Spinal cord; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Interleukin-6 - genetics; Male; Matrix Metalloproteinase 3 - genetics; Medical sciences; Nervous system (semeiology, syndromes); Neurology; Polymorphism, Genetic; Promoter Regions, Genetic - genetics; Scoliosis - genetics; Tumors of the nervous system. Phacomatoses
• ISSN: 0362-2436; 1528-1159
• DOI: 10.1097/BRS.0b013e31815a5943

Case-control study. As inflammation plays a key role in the etiology of intervertebral disc degeneration, we suggest a possible contribution of pro-inflammatory gene polymorphisms in the pathogenesis of adolescent idiopathic scoliosis (AIS). The nucleus pulposus of scoliotic discs responds to exogenous stimuli by secreting interleukin-6 (IL-6) and other inflammatory cytokines. The association between matrix metalloproteinases (MMPs) and disc degeneration has been reported by several investigators. A human MMP-3 promoter 5A/6A gene polymorphism regulates MMP-3 genes expression, while the G/C polymorphism of the promoter region of IL-6 gene influences levels and functional activity of the IL-6 protein. We conducted a case-control study to investigate whether the 5A/6A polymorphism of the MMP-3 gene and the G/C polymorphism of the promoter region of IL-6 gene were associated with susceptibility to AIS. The frequency of the 5A/5A genotype of MMP-3 gene polymorphism in patients with scoliosis was almost 3 times higher than in controls (30.2% vs. 11.2%, p 0.001), and the frequency of the G/G genotype of IL-6 gene polymorphism in patients with scoliosis was almost 2 times higher than in controls (52.8% vs. 26.2%, P < 0.001). 5A/5A genotype of MMP-3 gene polymorphism and G/G genotype of IL-6 gene polymorphism are independently associated with a higher risk of scoliosis (odds ratio, respectively, 3.34 and 10.54). This is the first study that has evaluated the possibility that gene variants of IL-6 and MMPs might be associated with scoliosis and suggests that MMP-3 and IL-6 promoter polymorphisms constitute important factors for the genetic predisposition to scoliosis.