Yang Jie, Wang Junhu, Liang Xiaojun, Zhao Hongmou, Lu Jun, Ma Qiang, Tian Feng
Department of Foot and Ankle Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China.
Genet Test Mol Biomarkers. 2019 Jun;23(6):380-386. doi: 10.1089/gtmb.2018.0269. Epub 2019 May 7.
Hallux valgus (HV) is a type of forefoot deformity affecting ∼23% of adults. Previous studies have shown that HV is highly heritable. Tumor necrosis factor () is an important proinflammatory cytokine involved in bone remodeling and plays essential roles in osteoarthritis and chronic inflammatory bone diseases, including HV. A total of 1,788 Chinese women comprising 637 HV subjects and 1,151 controls were recruited. Twelve single nucleotide polymorphisms (SNPs) located in and its promoter regions were selected and genotyped. Genetic association analyses were performed to investigate potential susceptibility SNPs. Bioinformatic and expression quantitative trait loci (eQTL) analyses were conducted to examine the functional consequences of the SNPs identified as being significantly associated with HV. SNP rs1800629, which is located at the 5' end of the promoter region of , was identified as significantly associated with HV status in Chinese women (OR = 0.56, = 2.12 × 10). Bioinformatic analyses using RegulomeDB indicated that this SNP has important functional significance, but subsequent eQTL analyses did not identify a significant association between rs1800629 and TNF gene expression. In addition, 26 genes with cis-eQTL for rs1800629 were identified. This study identified a susceptibility SNP for HV located within the promoter region of the gene. Bioinformatic and eQTL analyses linked this SNP to 26 genes but not to . Functional studies are needed to more fully characterize the effects of this SNP.
拇外翻（HV）是一种影响约23%成年人的前足畸形。先前的研究表明，HV具有高度遗传性。肿瘤坏死因子（TNF）是一种参与骨重塑的重要促炎细胞因子，在骨关节炎和慢性炎性骨病（包括HV）中起重要作用。共招募了1788名中国女性，其中包括637名HV患者和1151名对照。选择位于TNF及其启动子区域的12个单核苷酸多态性（SNP）进行基因分型。进行遗传关联分析以研究潜在的易感SNP。进行生物信息学和表达数量性状位点（eQTL）分析以检查被鉴定为与HV显著相关的SNP的功能后果。位于TNF启动子区域5'端的SNP rs1800629被鉴定为与中国女性的HV状态显著相关（OR = 0.56，P = 2.12×10）。使用RegulomeDB进行的生物信息学分析表明，该SNP具有重要的功能意义，但随后的eQTL分析未发现rs1800629与TNF基因表达之间存在显著关联。此外，鉴定出26个具有rs1800629顺式eQTL的基因。本研究在TNF基因启动子区域内鉴定出一个HV易感SNP。生物信息学和eQTL分析将该SNP与26个基因相关联，但未与TNF相关联。需要进行功能研究以更全面地表征该SNP的作用。
