Relationship Between Genetic Polymorphisms of the TNF Gene and Hallux Valgus Susceptibility.
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 (TNF) 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 TNF 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 TNF, was identified as significantly associated with HV status in Chinese women (OR = 0.56, p = 2.12 × 10-6). 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 TNF gene. Bioinformatic and eQTL analyses linked this SNP to 26 genes but not to TNF. Functional studies are needed to more fully characterize the effects of this SNP.
['Yang|Jie|J|', 'Wang|Junhu|J|', 'Liang|Xiaojun|X|', 'Zhao|Hongmou|H|', 'Lu|Jun|J|', 'Ma|Qiang|Q|', 'Tian|Feng|F|']
D000328:Adult D000483:Alleles D044466:Asians D016022:Case-Control Studies D002681:China D005006:Ethnicity D005260:Female D020022:Genetic Predisposition to Disease D014644:Genetic Variation D005838:Genotype D006215:Hallux Valgus D006239:Haplotypes D006801:Humans D008875:Middle Aged D020641:Polymorphism, Single Nucleotide D040641:Quantitative Trait Loci D012307:Risk Factors D014409:Tumor Necrosis Factor-alpha
hallux valgus susceptibility single nucleotide polymorphisms genetic association tumor necrosis factor gene