Inner Mongolia Medical University, Hohhot, China.
Department of thoracolumbar spine surgery, The Second Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China.
Mol Genet Genomic Med. 2019 Jul;7(7):e00747. doi: 10.1002/mgg3.747. Epub 2019 May 20.
Lumbar disk herniation (LDH) is a degenerative disorder, which partly results from complex genetic factors. The aim of the study was to investigate the potential associations between glypican-6 (GPC6) variants and LDH risk in Han Chinese population.
A total of 508 Han Chinese LDH patients and 508 healthy controls were recruited in this study. Six single-nucleotide polymorphisms (SNPs) in GPC6 were selected and genotyped using an Agena MassARRAY platform. We used logistic regression method to evaluate the linkage between GPC6 variants and LDH risk by calculating the odds ratio (OR) and 95% confidence intervals (CIs) in multiple genetic models. HaploReg database was used for SNP functional annotation.
Our result revealed GPC6 rs4773724 was associated with a decreased risk of LDH in allele model (OR = 0.82, 95% CI: 0.68-0.98, p = 0.026), whereas rs1008993 increased the LDH risk (OR = 1.34, 95% CI: 1.05-1.71, p = 0.020). Besides, we also found rs4773724 and rs9523981 were associated with susceptibility of LDH among individuals whose age are less than 45. And rs1008993 was associated with increased LDH risk in males. Furthermore, Haplotype analysis showed that the TT (rs4773724, rs1008993) haplotype and GC (rs4773724, rs1008993) haplotype had the opposite effects on the susceptibility of LDH.
For the first time, we suggest that rs4773724 and rs1008993 in GPC6 were considered as a protective factor and a risk factor for LDH in Han Chinese population, respectively. These results provide new ideas for the treatment and prevention of LDH in Han Chinese population.
腰椎间盘突出症(LDH)是一种退行性疾病,部分原因是复杂的遗传因素。本研究的目的是探讨 GPC6 变异与汉族人群 LDH 风险的潜在关联。
本研究共纳入 508 例汉族 LDH 患者和 508 例健康对照。使用 Agena MassARRAY 平台对 GPC6 中的 6 个单核苷酸多态性(SNP)进行了基因分型。我们使用逻辑回归方法,通过计算多种遗传模型中的比值比(OR)和 95%置信区间(CI),来评估 GPC6 变异与 LDH 风险之间的连锁关系。HaploReg 数据库用于 SNP 功能注释。
我们的结果显示,GPC6 的 rs4773724 等位基因模型与 LDH 风险降低相关(OR=0.82,95%CI:0.68-0.98,p=0.026),而 rs1008993 增加了 LDH 风险(OR=1.34,95%CI:1.05-1.71,p=0.020)。此外,我们还发现 rs4773724 和 rs9523981 与 45 岁以下人群的 LDH 易感性相关,rs1008993 与男性 LDH 风险增加相关。此外,单体型分析显示,rs4773724、rs1008993 的 TT 单体型和 rs4773724、rs1008993 的 GC 单体型对 LDH 的易感性有相反的影响。
我们首次发现 GPC6 中的 rs4773724 和 rs1008993 被认为是汉族人群 LDH 的保护因素和风险因素。这些结果为汉族人群 LDH 的治疗和预防提供了新的思路。