Analysis of single nucleotide polymorphism in adolescent idiopathic scoliosis in Korea: for personalized treatment

Abstract

Purpose: The incidence of adolescent idiopathic scoliosis (AIS) has rapidly increased, and with it, physician consultations and expenditures (about one and a half times) in the last 5 years. Recent etiological studies reveal that AIS is a complex genetic disorder that results from the interaction of multiple gene loci and the environment. For personalized treatment of AIS, a tool that can accurately measure the progression of Cobb's angle would be of great use. Gene analysis utilizing single nucleotide polymorphism (SNP) has been developed as a diagnostic tool for use in Caucasians but not Koreans. Therefore, we attempted to reveal AIS-related genes and their relevance in Koreans, exploring the potential use of gene analysis as a diagnostic tool for personalized treatment of AIS therein.

Materials and methods: A total of 68 Korean AIS and 35 age- and sex-matched, healthy adolescents were enrolled in this study and were examined for 10 candidate scoliosis gene SNPs.

Results: This study revealed that the SNPs of rs2449539 in lysosomal-associated transmembrane protein 4 beta (LAPTM4B) and rs5742612 in upstream and insulin-like growth factor 1 (IGF1) were associated with both susceptibility to and curve severity in AIS. The results suggested that both LAPTM4B and IGF1 genes were important in AIS predisposition and progression.

Conclusion: Thus, on the basis of this study, if more SNPs or candidate genes are studied in a larger population in Korea, personalized treatment of Korean AIS patients might become a possibility.

Fig. 1

(A) A female patient (8 years 1 month) when first discovered in had a Cobb's of 12.5 degrees. She was kept under observation but the Cobb's angle deteriorated to 27 degrees. Therefore, she was treated with brace and exercise. After 2 years and 4 months of non-surgical treatment, Cobb's angle improved to 11.4 degrees. (B) Female patient (8 years 5 month) when first diagnosed, had 27.5 degrees Cobb's and was treated with brace and exercise but the Cobb's angle deteriorated to 140 degrees. Finally, her scoliosis and pulmonary functions deteriorated enough to cause serious danger to her life.

Fig. 2

Reviewing the relation between rs2449539 SNP and the Cobb's angle, genotype TT was compared with the CC, TC type and a significant difference (p=0.0028) was found. Comparison between CC type and TT type also showed a significant difference (p=0.0071). SNP, single nucleotide polymorphism.