Association between IL-6 and MMP-3 gene polymorphisms and adolescent idiopathic scoliosis: a case-control study.
METHODS
Case-control study.


OBJECTIVE
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).


BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Aulisa
Lorenzo
L
A. Gemelli University Hospital, 8, Rome, Italy.
Papaleo
Pierangelo
P
Pola
Enrico
E
Angelini
Flavia
F
Aulisa
Angelo G
AG
Tamburrelli
Francesco C
FC
Pola
Paolo
P
Logroscino
Carlo A
CA
D000293:Adolescent; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012600:Scoliosis / Q000235:genetics*
D015850:Interleukin-6; D019278:Matrix Metalloproteinase 3