Study design: A genetic association study of leptin receptor (LEPR) gene with adolescent idiopathic scoliosis (AIS) in the Chinese Han population.
Objective: To determine whether LEPR gene polymorphisms are associated with the predisposition and/or disease severity of AIS.
Summary of background data: Patients with AIS were reported to have lower body mass index (BMI), abnormal leptin bioavailability, and systemic lower bone mass, which implied that leptin/LEPR signaling pathway may be implicated in the etiology of AIS. Previous association study of the polymorphisms in leptin gene did not show significant differences between AIS cases and controls. However, no study has been done to investigate the relationship between genetic polymorphisms of the LEPR gene and susceptibility to AIS.
Methods: 570 patients with AIS aged 10 to 18 years were enrolled, and 570 age-matched healthy subjects were recruited as controls. 6 single nucleotide polymorphisms (SNPs) (rs1137101, rs1137100, rs4655555, rs2767485, rs1751492, and rs8179183) of LEPR gene were selected. The polymorphisms were genotyped using the polymerase chain reaction (PCR)-based Invader assay. Case-control study was performed to define the contribution of the 6 SNPs to predisposition of AIS. 1-way analysis of variance (ANOVA) test was used to compare the mean Cobb angles and BMI among patients with different genotypes in case-only analyses. Statistical significance was set at P < 0.05.
Results: Both the genotype and allele frequencies of SNP rs2767485 were significantly different between the patient with AIS and the control groups. No significant difference of allele frequency was noted in other 5 SNPs between the patients with AIS and the normal controls. Both the mean maximum Cobb angles and BMI of different genotype AIS groups were similar to each other for all the 6 SNPs (P > 0.05).
Conclusion: Polymorphism of rs2767485 in LEPR gene is associated with the occurrence of AIS, suggesting LEPR is a predisposition gene.