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Purpose: This study was aimed to discover the combined effects of single nucleotide polymorphisms (SNPs) within the C-reactive protein (CRP) gene and potential environmental factors on the risk and prognosis for diabetic foot osteomyelitis (DFO)., Methods: A total of 1734 diabetes mellitus patients, 681 with DFO and 1053 without DFO, were successfully recruited, as well as 1261 healthy control individuals. Participants data were recorded regarding age, gender, smoking and drinking history, body mass index (BMI), hypertension, cacosmia, and ulceration. A total of 11 SNPs within the CRP gene were designated for exploration, by logistic regression analyses, of how they might interact with environmental factors to affect susceptibility to DFO., Results: Frequencies of smoking and drinking, and incidence of hypertension, cacosmia, or ulceration displayed marked differences (all P <0.05) between DFO and non-DFO patients. Furthermore, allele G of rs11265260 (A>G), allele G of rs1800947 (C>G), and allele T of rs3093059 (T>C) and rs1130864 (C>T) exhibited a trend to increase risk of DFO (all P <0.05). Allele G of rs11265260 (A>G), allele G of rs1800947 (C>G) and rs3093068 (G>C), and allele T of rs1130864 (C>T) were significant predictors of poor prognosis among DFO patients ( P <0.05). In addition, genotypes of rs11265260 (i.e., GG and AG), rs1800947 (i.e., CG and GG), rs3093059 (i.e., TT) and rs113084 (i.e., CT and TT) amplified the influence of smoking, alcohol consumption, cacosmia, and ulceration on progression from non-DFO to DFO (all γ >1)., Conclusion: Genetic mutations within CRP functioned interactively with external factors to affect DFO risk., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

BACKGROUND Worldwide, the treatment of complications associated with type 2 diabetes mellitus, including diabetic foot ulcer (DFU), results in an economic burden for patients and healthcare systems. This study aimed to use high-throughput 16S rRNA gene sequencing to investigate the changes in foot skin microbiome of patients with diabetes mellitus from a single center in China. MATERIAL AND METHODS Fifty-two participants were divided into 4 study groups: healthy controls (n=13); patients with short-term diabetes (<2 years; n=13); patients with intermediate-term diabetes (5-8 years; n=13); and patients with long-term diabetes (>10 years; n=13). Swabs were analyzed from the intact skin of the foot arch using high-throughput 16S ribosomal RNA sequencing. RESULTS Microbiome phylogenic diversity varied significantly between the study groups (whole tree, P<0.01; Chao1, P<0.01), but were similar within the same group. The findings were supported by non-parametric multidimensional scaling (stress=0.12) and principal component analysis (principal component 1, 8.38%; principal component 2, 5.28%). In patients with diabetes mellitus, the dominant skin microbial phyla were Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes. CONCLUSIONS High-throughput 16S rRNA gene sequencing showed dynamic changes in the skin microbiome from the foot during the progression of diabetes mellitus. These findings support the importance of understanding the role of the skin microbiota in the pathogenesis of DFU.