Genetic Determinants for Bacterial Osteomyelitis: A Focused Systematic Review of Published Literature

Abstract

Background: Osteomyelitis is an inflammatory process characterized by progressive bone destruction. Moreover, chronic bacterial osteomyelitis is regarded as a difficult-to-treat clinical entity due to its long-standing course and frequent infection recurrence. However, the role of genetic factors in the occurrence and development of bacterial osteomyelitis is poorly understood.Methods: We performed a systematic review to assess the frequency of individual alleles and genotypes of single-nucleotide polymorphisms (SNPs) among patients with bacterial osteomyelitis and healthy people to identify whether the SNPs are associated with the risk of developing bacterial osteomyelitis. Then, gene ontology and Kyoto Encyclopedia of Gene and Genomes analyses were performed to identify the potential biological effects of these genes on the pathogenesis of bacterial osteomyelitis.Result: Fourteen eligible studies containing 25 genes were analyzed. In this review, we discovered that the SNPs in IL1B, IL6, IL4, IL10, IL12B, IL1A, IFNG, TNF, PTGS2, CTSG, vitamin D receptor (VDR), MMP1, PLAT, and BAX increased the risk of bacterial osteomyelitis, whereas those in IL1RN and TLR2 could protect against osteomyelitis. The bioinformatic analysis indicated that these osteomyelitis-related genes were mainly enriched in inflammatory reaction pathways, suggesting that inflammation plays a vital role in the development of bacterial osteomyelitis. Furthermore, functional notation for 25 SNPs in 17 significant genes was performed using the RegulomeDB and NCBI databases. Four SNPs (rs1143627, rs16944, rs2430561, and rs2070874) had smaller scores from regulome analysis, implying significant biological function.Conclusion: We systematically summarized several SNPs linked to bacterial osteomyelitis and discovered that these gene polymorphisms could be a genetic factor for bacterial osteomyelitis. Moreover, further large-scale cohort studies are needed to enhance our comprehensive understanding of the development of osteomyelitis to provide earlier individualized preventions and interventions for patients with osteomyelitis in clinical practice.

Bone and joint infection complicated with sepsis in neonates and infants under three months of age

“…Genetic polymorphisms in the immune response to infection have been shown to be associated with sepsis and bacterial osteomyelitis; this needs further research. 29 , 30 …”

Exploring the pathogenesis of osteomyelitis accompanied by diabetic foot ulcers using microarray data analysis

“…Osteoblasts increase MMP1 expression under the regulation of IL-1 alpha, that the frequency of MMP1 (-1607 2G/2G) genotype in OM patients exhibits, resulting in increased levels of MMP1 2G allele in OM patients, and further promoting local healing of osteomyelitis. [ 31 ] In addition, it has also been discovered that MMP1 can contribute to a reduced risk of osteomyelitis. [ 32 ] In wound healing of DFU, a variety of cells, including fibroblasts, basal cells, and vascular endothelial cells, express MMP1.…”

Bone Involvement in Systemic Lupus Erythematosus

“…Despite appropriate treatments, up to 30% of OM cases become chronic, resulting in serious morbidity and disability and remarkable economic burden [ 66 ]; a genetic predisposing substrate may partly explain these results. Recently, Xie et al analyzed several single-nucleotide polymorphisms (SNPs) of DNA sequences linked to the susceptibility of OM and they reported that the SNPs in IL1B , IL6 , IL4 , IL10 , IL12B , IL1A , IFNG , TNF , PTGS2 (prostaglandin-endoperoxide synthase 2), CTSG (cathepsin G), VDR (vitamin D receptor), MMP1 (matrix metalloproteinase 1), PLAT (plasminogen activator, tissue type), and BAX (Bcl-2 associated X) increased the risk of bacterial OM, whereas those in IL1RN (IL-1 receptor antagonist) and TLR2 (toll-like receptor 2) could protect against OM [ 66 ]. These OM-related genes encode for cytokines, enzymes and proteins involved in inflammatory pathways and in host defense against pathogenic microorganisms, suggesting that inflammation plays a pivotal role in OM development.…”