Study design: A case-control study.
Objective: To validate the relationship between POC5 and adolescent idiopathic scoliosis (AIS) in the Chinese patients and to further investigate the functional role of POC5.
Summary of background data: Three rare functional variants in the POC5 were recently reported to be strongly associated with the disease in a large family with multiple members affected with idiopathic scoliosis. To our knowledge, the association between the mutations of POC5 and AIS remains undetermined in the Chinese population.
Methods: Single nucleotide variants c.1336G>A, c.1286C>T, and c.1363G>C of POC5 were genotyped in 2432 patients with AIS and 2292 healthy controls using multiple ligase detection reactions. Common variants covering POC5 gene were genotyped in 1446 patients and 2080 controls. The mRNA expression of POC5 was determined in the paraspinal muscles collected from 98 patients and 28 controls. The Student t test was used to compare mRNA expression level between the patients and the controls. In addition, the POC5 expression was compared among different genotypes of the remarkably associated single nucleotide polymorphism (SNP) with analysis of variance test.
Results: There was no case of mutation for the three reported variants of POC5. SNP rs6892146 was observed to have significantly different distribution of minor allele frequency in the two group (0.485 vs. 0.446, P = 0.004). The mRNA expression of POC5 was 1.5-fold higher in patients than in the controls (0.00012 ± 0.00009 vs. 0.00008 ± 0.00006, P = 0.02). Patients with genotype GG have a significantly increased expression of POC5 than those with CC (0.00014 ± 0.00007 vs. 0.00009 ± 0.00007, P = 0.03).
Conclusion: Common variant rs6892146 of POC5 is associated with the development of AIS in the Chinese population. Targeted regional sequencing of POC5 may help identify novel mutations associated with AIS.
Level of evidence: 4.