SH Ho Scoliosis Research Laboratory, Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR.
Department of Obstetrics and Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR.
Spine (Phila Pa 1976). 2019 Apr 1;44(7):464-471. doi: 10.1097/BRS.0000000000002866.
A genetic association (replication) study.
The aim of this study was to replicate and further evaluate the association among seven genome-wide association studies (GWAS)-identified single nucleotide polymorphisms (SNPs) in Chinese girls with adolescent idiopathic scoliosis (AIS) with disease onset, curve types, and progression.
AIS is the most common pediatric spinal deformity with a strong genetic predisposition. Recent GWAS identified 10 new disease predisposition loci for AIS.
Three hundred nineteen female AIS patients with Cobb angle ≥ 10 and 201 healthy controls were studied for the association with disease onset. Seven GWAS-identified SNPs (rs11190870 in LBX1, rs12946942 in SOX9/KCNJ2, rs13398147 in PAX3/EPH4, rs241215 in AJAP1, rs3904778 in BNC2, rs6570507 in GPR126, and rs678741 in LBX1-AS1) were analyzed. In subgroup analysis, AIS patients were subdivided by curve types and disease progression to examine for genotype association.
We replicated the association with disease onset in four common SNPs rs11190870, rs3904778, rs6570507, and rs678741. In addition, rs1190870 and rs678741 remained significantly associated in the right thoracic curves only subgroup. However, no significant difference was observed with both clinical curve progression or Cobb angle.
This study replicated the associations of four GWAS-associated SNPs with occurrence of AIS in our Chinese population. However, none of these SNPs was associated with curve severity and progression. The results suggest that curve progression may be determined by environmental (nongenetic) factor, but further study with a larger sample size is required to address this issue.
遗传关联（复制）研究。
本研究旨在复制并进一步评估在中国少女特发性脊柱侧凸（AIS）患者中，与疾病发病、曲线类型和进展相关的 7 项全基因组关联研究（GWAS）确定的单核苷酸多态性（SNP）之间的关联。
AIS 是最常见的儿科脊柱畸形，具有很强的遗传易感性。最近的 GWAS 确定了 10 个新的 AIS 疾病易感性位点。
研究了 319 名 Cobb 角≥10 的女性 AIS 患者和 201 名健康对照者与疾病发病的相关性。分析了 7 个 GWAS 确定的 SNP（LBX1 中的 rs11190870、SOX9/KCNJ2 中的 rs12946942、PAX3/EPH4 中的 rs13398147、AJAP1 中的 rs241215、BNC2 中的 rs3904778、GPR126 中的 rs6570507 和 LBX1-AS1 中的 rs678741）。在亚组分析中，根据曲线类型和疾病进展对 AIS 患者进行细分，以检查基因型相关性。
我们复制了 rs11190870、rs3904778、rs6570507 和 rs678741 这四个常见 SNP 与发病的关联。此外，rs1190870 和 rs678741 仅在右胸曲组中仍与显著相关。然而，无论是临床曲线进展还是 Cobb 角都没有观察到显著差异。
本研究在我国人群中复制了 4 个与 GWAS 相关的 SNP 与 AIS 发病的关联。然而，这些 SNP 均与曲线严重程度和进展无关。结果表明，曲线进展可能由环境（非遗传）因素决定，但需要进一步的研究来解决这个问题。
4 级。
