A Promoter Polymorphism of Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) Gene Is Associated With Severity of Thoracic Adolescent Idiopathic Scoliosis.

By London Spine

A Promoter Polymorphism of Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) Gene Is Associated With Severity of Thoracic Adolescent Idiopathic Scoliosis.

Spine (Phila Pa 1976). 2011 Jan 11;

Authors: Jiang J, Qian B, Mao S, Zhao Q, Qiu X, Liu Z, Qiu Y

ABSTRACT: Study Design: A genetic association study of tissue inhibitor of metalloproteinase-2 (TIMP-2) gene with adolescent idiopathic scoliosis (AIS) in a Chinese population.Objective: To determine whether a promoter polymorphism of TIMP-2 gene correlates with the occurrence and curve severity of AIS patients.Summary of Background Data: Previous studies have suggested that genetic factors play an important role in etiology of AIS. The relative anterior spinal column overgrowth due to abnormal endochondral ossification has been considered to be a significant factor in etiopathogenesis of AIS. The specific role of matrix metalloproteases (MMPs) and their activity inhibitors (Tissue Inhibitor of Metalloproteinases, TIMPs) during endochondral ossification has been documented. TIMP-2 is the major TIMP expressed during bone development, and TIMP-2 gene is located in one of chromosomal regions linked to AIS. Therefore, TIMP-2 gene is a potential candidate gene for AIS.Methods: This study included a total of 570 female AIS patients, who were divided into two groups according to curve patterns. 354 patients with right thoracic curve were in group A (326 cases with Lenke 1 type and 28 cases with Lenke 2 type), while 216 patients with a single lumber curve were in group B (216 cases with Lenke 5 type). 210 age-matched healthy girls were recruited as normal controls. One SNP-418G/C (rs8179090) in the promoter region were selected for TIMP-2 gene. Genotyping was performed by PCR-restriction fragment length polymorphism in each group respectively.Results: No significant differences of genotype and allele frequency distribution were found between AIS patients and normal controls either in group A or in group B. The frequency of C allele was significantly higher in patients with Cobb angle ?40° compared with those with Cobb angle <40° in group A (P<0.05), while this difference was not noted in group B (P>0.05). Among the patients who reached skeletal maturity without any interference of natural history, significantly higher average maximum Cobb angle was found in patients with C allele compared with those without C allele in group A (P<0.05). However, in group B, the mean maximum Cobb angle were similar between patients with different genotypes in both cases with left-side curves and cases with right-side curves (P>0.05). Furthermore, for the patients whose values of thoracic kyphosis (TK) were recorded, those with C allele had smaller average TK than those without C allele in Group A (P<0.05). However, such significant difference was not observed in Group B.Conclusion: The SNP-418G/C (rs8179090) in the promoter region of TIMP-2 gene was not associated with the occurrence of AIS. However, it may predict curve severity of thoracic AIS. Hence, TIMP-2 gene is a disease-modifier gene of thoracic AIS.

PMID: 21228746 [PubMed – as supplied by publisher]