A Novel Coding Variant in SLC39A8 Is Associated With Adolescent Idiopathic Scoliosis in Chinese Han Population.

STUDY

DESIGN

A genetic case-control association study.

OBJECTIVE

The aim of this study was to investigate the association of SLC39A8 with the susceptibility of adolescent idiopathic scoliosis (AIS) in Chinese Han population.

SUMMARY OF BACKGROUND DATA: A recent exome-wide association study identified a missense variant rs13107325 in SLC39A8 that was associated with AIS. However, there was a lack of study validating the association of this novel mutation with AIS in other populations.

METHODS

The variant rs13107325 was genotyped in 965 AIS patients and 976 healthy controls by allelic specific multiple ligase detection reactions. Variants located in the coding region of SLC39A8 were identified by exon sequencing for 192 AIS patients and 192 controls. Paraspinal muscles from 36 AIS patients and 36 age-matched congenital scoliosis patients were collected for the gene expression analysis. Comparison between the cases and controls was performed with the χ test for genotyping data or with Student t test for gene expression analysis.

RESULTS

For the missense variant rs13107325, there was no case of mutation detected in the patients or the controls. All the subjects had homozygous genotype CC. Exon sequencing revealed that a coding variant rs11097773 of SLC39A8 had a significantly different distribution of minor allele frequency between patients and controls (7.81% vs. 14.8%, P = 0.002). The mRNA expression of SLC39A8 in the patients was remarkably lower than that in the controls (0.0015 ± 0.00026 vs. 0.0021 ± 0.00033, P < 0.001).

CONCLUSION

The association of previously reported novel mutation (rs13107325 in SLC39A8) with AIS was not replicated in the Chinese population. Interestingly, a novel coding variant rs11097773 of SLC39A8 is found significantly associated with AIS. Moreover, the expression of SLC39A8 was obviously decreased in AIS patients. Further study is warranted to clarify the functional role of rs11097773 in the development of AIS.

LEVEL OF EVIDENCE: 3.