National Research Centre Kurchatov Institute, Moscow, Russian Federation.
Pirogov Russian National Research Medical University, Moscow, Russian Federation.
Endocrine. 2024 Dec;86(3):1035-1044. doi: 10.1007/s12020-024-03966-2. Epub 2024 Jul 17.
Diabetic foot ulcer (DFU) is one of the most severe complications of type 2 diabetes, which is manifested in chronic skin ulcers of lower extremities. DFU treatment remains complex and expensive despite the availability of well-established protocols. Early prediction of potential DFU development at the onset of type 2 diabetes can greatly improve the aftermath of this complication.
To assess potential genetic markers for DFU, a group of diabetic patients from Moscow region with and without DFU was genotyped for a number of SNPs previously reported to be associated with the DFU.
Obtained results did not confirm previously claimed association of rs1024611, rs3918242, rs2073618, rs1800629, rs4986790, rs179998, rs1963645 and rs11549465 (respectively, in MCP1, MMP9, TNFRSF11B, TNFα, TLR4, eNOS, NOS1AP and HIF1α genes) with the DFU. Surprisingly, the t allele of rs7903146 in the TCF7l2 gene known as one of the most prominent risk factors for type 2 diabetes has shown a protective effect on DFU with OR(95%) = 0.68(0.48-0.96).
Non-replication of previously published SNP associations with DFU suggests that the role of genetic factors in the DFU onset is either highly variable in different populations or is not as significant as the role of non-genetic factors.
糖尿病足溃疡(DFU)是 2 型糖尿病最严重的并发症之一,表现为下肢慢性皮肤溃疡。尽管有成熟的治疗方案,但 DFU 的治疗仍然复杂且昂贵。在 2 型糖尿病发病时早期预测潜在的 DFU 发展,可以极大地改善这种并发症的后果。
为了评估潜在的 DFU 遗传标志物,对来自莫斯科地区的一组有和无 DFU 的糖尿病患者进行了一系列先前报道与 DFU 相关的 SNP 基因分型。
所获得的结果并未证实 rs1024611、rs3918242、rs2073618、rs1800629、rs4986790、rs179998、rs1963645 和 rs11549465(分别在 MCP1、MMP9、TNFRSF11B、TNFα、TLR4、eNOS、NOS1AP 和 HIF1α 基因中)与 DFU 的先前声称的关联。令人惊讶的是,TCF7l2 基因中 rs7903146 的 t 等位基因,作为 2 型糖尿病的最显著危险因素之一,对 DFU 具有保护作用,OR(95%)=0.68(0.48-0.96)。
先前发表的 SNP 与 DFU 关联的非复制结果表明,遗传因素在 DFU 发病中的作用在不同人群中差异很大,或者不如非遗传因素的作用重要。