Polymorphisms in paired box 1 gene were associated with susceptibility of adolescent idiopathic scoliosis: A case-control study

Abstract

Background: Association of genetic polymorphisms in paired box 1 (PAX-1) gene can influence the development of adolescent idiopathic scoliosis (AIS). PAX-1 is mainly expressed in the region of the vertebral bodies and intervertebral discs, being important for the proper formation of spinal structures.

Objectives: The objective of this study was to evaluate the association of polymorphisms in PAX-1 gene with the susceptibility of AIS.

Settings and design: This was an analytical observational case-control study.

Materials and methods: Samples of 59 AIS indicated for surgical treatment, and 119 controls, without spinal disease were genotyped for PAX-1 rs6137473 and rs169311 polymorphisms.

Statistical analysis: The association of the polymorphisms with AIS was evaluated by a multivariable logistic regression model, using odds ratios (OR) and 95% confidence intervals (CI).

Results: According to Lenke's classification, 89.8% had Type I and 10.2% II curves. The mean value of the Cobb angle of the proximal thoracic curve was 30.8°, 58.7° thoracic, and 30.4° for the lumbar and on the bending films 14.6°, 40.7°, and 11°, respectively. Among the AIS group, there was a predominance of females (8.8:1). The PAX-1 rs169311 and rs6137473 polymorphisms were positively associated with developing the AIS (OR = 1.98; 95% CI = 1.2-3.3 and OR = 3.16; 95% CI = 1.4-7.3, respectively). The rs6137473 polymorphism was associated with the lumbar modifier B and C compared to A (OR = 2.52; 95% CI = 1.1-5.8).

Conclusions: PAX-1 polymorphisms were associated with an increased risk of developing the AIS and with curve severity and can be used as a biomarker to map the risk of developing surgical-grade AIS, guiding the treatment of patients.

Keywords: Adolescent idiopathic scoliosis; Lenke's classification; genetic polymorphisms; paired box 1.

Figure 1

Spine radiographs of scoliosis patients. (a-d) Cobb angle measurements. (a) Posteroanterior radiograph with proximal thoracic (white lines), main thoracic (red lines), and thoracolumbar curves (yellow lines) measured. (b) Left-side bending radiograph showing proximal thoracic (white lines) and thoracolumbar flexibility (black lines). (c) Right-side bending radiograph showing main thoracic curve flexibility. (d) Lateral spine radiograph showing thoracic kyphosis measured from T5 to T12

Figure 2

Adolescent idiopathic scoliosis patients (n = 59) distribution categorized by Lenke's classification system. A, B, and C are the lumbar spine modifier. Type Lenke I main thoracic and Lenke II double thoracic curves

Figure 3

Allelic and genotypic distribution of the PAX-1 polymorphisms in adolescent idiopathic scoliosis cases and controls (n = 178). P value calculated by Chi-square test or Fisher's exact test, when necessary. PAX-1 - Paired box 1