A Genetic Variant of FAM46A is Associated With the Development of Adolescent Idiopathic Scoliosis in the Chinese Population

Abstract

Study design: A genetic case-control study.

Objective: To replicate recently reported genetic loci associated with adolescent idiopathic scoliosis (AIS) in the Chinese Han population, and to determine the relationship between gene expression and the clinical features of the patients.

Summary of background data: A recent study conducted in the Japanese population identified several novel susceptible loci, which might provide new insights into the etiology of AIS. However, the association of these genes with AIS in other populations remains unclear.

Materials and methods: A total of 1210 AIS and 2500 healthy controls were recruited for the genotyping of 12 susceptibility loci. Paraspinal muscles used for gene expression analysis were obtained from 36 AIS and 36 patients with congenital scoliosis. The difference regarding genotype and allele frequency between patients and controls was analyzed by χ 2 analysis. The t test was performed to compare the target gene expression level between controls and AIS patients. Correlation analysis was performed between gene expression and phenotypic data, including Cobb angle, bone mineral density, lean mass, height, and body mass index.

Results: Four SNPs, including rs141903557, rs2467146, rs658839, and rs482012, were successfully validated. Allele C of rs141903557, allele A of rs2467146, allele G of rs658839, and allele T of single nucleotide polymorphism rs482012 showed significantly higher frequency in patients. Allele C of rs141903557, allele A of rs2467146, allele G of rs658839, and allele T of rs482012 could notably increase the risk of AIS patients, with an odds ratio of 1.49, 1.16, 1.11, and 1.25, respectively. Moreover, tissue expression of FAM46A was significantly lower in AIS patients as compared with controls. Moreover, FAM46A expression was remarkably correlated with bone mineral density of patients.

Conclusion: Four SNPs were successfully validated as novel susceptibility loci associated with AIS in the Chinese population. Moreover, FAM46A expression was associated with the phenotype of AIS patients.