Collagen I Alpha 2 Gene Polymorphism is Significantly Associated with Growth Disturbance in Adolescent Idiopathic Scoliosis

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• a - Scoliosis Research Society

Introduction: Abnormal peri-pubertal growth has been well reported and supported by our previous large scale study to be associated with the development of adolescent idiopathic scoliosis (AIS). In addition, low bone mineral density (BMD) as a phenotypic feature in AIS patients was also well recognized.

Type I collagen is the major protein scaffold in bone and play an important role in bone formation and mineralisation during growth. We hypothesized that collagen I alpha 2 (COL1A2) gene may be associated with abnormal phenotypic features observed in AIS patients. This study aims at investigating the association of the polymorphism of COL1A2 gene with anthropometric parameters and BMD in patients with AIS.

Methods: Fifty-six AIS girls aged 12-15 years (Cobb angle: 25.5 ± 8.4) underwent anthropometric (body weight, height and arm span) and BMD measurements. Corrected height was calculated from Bjure’s equation to adjust for lost of trunk height resulting from the scoliosis deformity. Anthropometric parameters and BMD of AIS patients were standardized as z-score with reference to 60 sex- and age-matched healthy adolescents. Peripheral blood samples were collected for study of the genotype of PvuII polymorphism of COL1A2 gene. Comparison of anthropometric parameters and BMD were tested by two-tailed student’s t-test. Pearson’s correlation was used to test the association between the parameters with COL1A2 polymorphism.

Results: Significantly longer arm span (z-score: 0.54±0.14) was found in the AIS group as compared to the controls (p=0.011). AIS group have significantly lower z-scores of weight (p=0.004) and BMI (p=0.001). There were significantly higher z-score of arm span in the combined group of AIS patients with PP or Pp genotype than those with pp genotype (p=0.025). Similar finding was found in corrected height of AIS patients (p=0.042). Moreover, anthropometric parameters of AIS patients showed significant association with the allelic variants of COL1A2 gene (pp < Pp < PP; r=0.295 & p=0.027 for arm span; r=0.284 & p=0.034 for corrected height). No association was found between anthropometric parameters and COL1A2 gene in the control groups.

AIS had significantly lower z-score of BMD than the control group, however, no association was found between BMD and COL1A2 gene in both AIS and the control groups.

Discussion: Growth disturbance and lower BMD were characterized as phenotypic features in AIS patients. The present results showed a significant association of COL1A2 polymorphism with longer arm span and taller stature, not with BMD, in AIS patients, suggesting COL1A2 gene might play an important role as modifiergene in the regulation of growth in AIS. This finding could be an important contribution to the understanding of the etio-pathogensis of AIS.

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