Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China (mainland).
Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing, China (mainland).
Med Sci Monit. 2018 Aug 12;24:5598-5609. doi: 10.12659/MSM.911101.
BACKGROUND The present study aimed to evaluate whether the fat mass and obesity-associated (FTO) gene polymorphisms are associated with risk of intervertebral disc degeneration (IDD) in a largest Chinese Han population. MATERIAL AND METHODS There were 502 IDD patients and 497 healthy controls enrolled in this study. Nineteen single nucleotide polymorphisms (SNPs) in the FTO gene were tested using the Sequenom MassARRAY platform. The Hardy-Weinberg equilibrium test, followed by allelic, genotypic, haplotypic association, and SNP interaction analyses were used for SNP evaluation. The Genotype-Tissue Expression (GTEx) database was used to evaluate expression quantitative trait loci (eQTL) value of polymorphism. Spearman rank correlation and logistic regression analyses were used for assessing the internal relation between genotypic changes and the risk of IDD. RESULTS Seventeen SNPs survived the Hardy-Weinberg equilibrium test. Allelic analysis showed that allele T of SNP rs1121980 was a risk allele. Haplotypic and SNP interaction analyses suggested that 2 haplotypes and 5 SNP combinations were associated with the predisposition of IDD respectively. GTEx database revealed that the SNP rs1121980 might interfere with the expression of the FTO gene in the muscle-skeletal system. Through clinical statistics analysis, the different genotypes of rs1121980 can present different disease severity of IDD. CONCLUSIONS Our study suggests that rs1121980 can become a biomarker for the screening and prognosis of IDD. The 2 haplotype blocks and 5 SNP-SNP combinations that we discovered might be indicative of the onset of IDD. Therefore, our study might serve as evidence for future IDD molecular diagnosis.
本研究旨在评估肥胖相关基因(FTO)多态性是否与中国汉族人群椎间盘退变(IDD)的风险相关。
本研究纳入了 502 例 IDD 患者和 497 例健康对照者。使用 Sequenom MassARRAY 平台检测 FTO 基因中的 19 个单核苷酸多态性(SNP)。采用 Hardy-Weinberg 平衡检验,然后进行等位基因、基因型、单倍型关联和 SNP 相互作用分析,对 SNP 进行评估。使用基因型组织表达(GTEx)数据库评估多态性的表达数量性状基因座(eQTL)值。采用 Spearman 秩相关和逻辑回归分析评估基因型变化与 IDD 风险之间的内在关系。
17 个 SNP 通过 Hardy-Weinberg 平衡检验。等位基因分析显示,SNP rs1121980 的 T 等位基因是风险等位基因。单倍型和 SNP 相互作用分析表明,2 个单倍型和 5 个 SNP 组合分别与 IDD 的易感性相关。GTEx 数据库显示,SNP rs1121980 可能干扰肌肉骨骼系统中 FTO 基因的表达。通过临床统计分析,rs1121980 的不同基因型可表现出不同的 IDD 严重程度。
本研究表明,rs1121980 可成为 IDD 筛查和预后的生物标志物。我们发现的 2 个单倍型块和 5 个 SNP-SNP 组合可能与 IDD 的发病有关。因此,本研究可能为未来的 IDD 分子诊断提供证据。