Study design: A genetic association study.
Objective: The aim of this study was to investigate whether NUCKS1 is a susceptible gene of adolescent idiopathic scoliosis (AIS) in Chinese population and to further narrate its association with the clinical phenotypes.
Summary of background data: AIS is characterized by late onset of menarche and disturbed growth rhythm. Previous studies showed that NUCKS1 is associated with age at menarche and pubertal height growth.
Methods: Single-nucleotide polymorphism rs951366 of NUCKS1 was genotyped in 972 patients and 1454 healthy controls. The differences of genotype and allele distributions between AIS patients and healthy controls were evaluated using the χ test. One-way analysis of variance test was used to compare the relationship between different genotypes and clinical features including tissue expression of NUCKS1, age at menarche, and curve magnitude.
Results: Patients were found to have a significantly lower frequency of CC than the controls (5.9% vs. 10.6%, P < 0.001). Besides, the frequency of allele C was found to be remarkably lower in the patients than the controls (26.4% vs. 30.9%, P < 0.001), with an odds ratio of 0.80 (95% confidential interval = 0.71-0.91). Patients with genotype CC had a remarkably lower age at menarche than patients with genotype TT (12.1 ± 1.7 vs. 12.8 ± 2.4 years, P = 0.02). Patients with genotype TT had a remarkably lower expression level of NUCKS1 than patients with genotype CC (2.8 ± 1.9 vs. 4.3 ± 2.2, P = 0.03). As for curve magnitude, no significant difference was found among patients with different genotypes.
Conclusion: Patients with allele T of rs951366 can be more vulnerable to the incidence of AIS as well as a late onset of menarche. Further functional analysis is warranted for a comprehensive knowledge on the contribution of this variant to the development of AIS.
Level of evidence: 4.