17A في المصل وتعدد اشكال جين الانترلوكين 34,17 A تقيم مستويات الانترلوكينات لدى مرضى تقرحات القدم السكري

Evaluation of Interleukins 17A, 34 Serum Levels and Interleukin 17A Gene polymorphism in Patients with Diabetic Foot Ulcer

Abstract

Diabetic foot ulcer (DFU) is a common and serious complication of diabetes mellitus, characterized by chronic infection and delayed wound healing. Interleukin-17A (IL-17A) is a pro-inflammatory cytokine, involved in immune regulation and tissue inflammation. The IL-17A gene contains a functional polymorphism at rs2275913 (-197 G>A), which may influence its expression and contribute to disease susceptibility. Interleukin-34 (IL-34) is another cytokine that regulates monocyte/macrophage activity and plays a key role in chronic inflammatory conditions. It acts through the colony-stimulating factor-1 (CSF-1) receptor and has been implicated in promoting tissue damage and impaired healing by enhancing inflammatory cell recruitment.
This case-control study included 100 participants divided into two groups:
a patient group comprising 50 individuals with diabetic foot ulcers who attended to Al-lmam Al-Hassan Center for Endocrinology and Diabetes in the holy city of Karbala during the period extended from December (2024) to March (2025) and the patients were previously diagnosed by doctors specialized in endocrinology and diabetes (34 males, 16 females; aged 35–78 years), and a control group of 50 healthy individuals (35 males, 15 females; aged 35–70 years).
Blood samples were collected from each participant, some of which were dispensed into two gel tubes used for laboratory test (Renal function test, Liver function test, Cholesterol, Triglyceride and Low-Density Lipoprotein (LDL) for patients) and enzyme-Linked Immunosorbent Assay (ELISA) analysis of IL-17A and IL-34 serum levels, while the remaining sample collected into two Ethylenediaminetetraacetic acid (EDTA) tube for hematological (CBC for all samples , and Hemoglobin Alc (HbA1C) for patients), and molecular testing, including IL-17A gene polymorphism analysis via allele-specific polymerase chain reaction PCR in 35 patients and 35 controls.
The present study results revealed that older age, family history, hypertension complication, duration within 10-20 years, and site of ulcer in fore foot were significantly (p< 0.05) associated with DFU. Also, significantly elevated serum levels of IL-17A (P = 0.017) and IL-34 (P = 0.0001) in DFU patients compared to controls, with AUC of IL-17A (0.638) and (0.743) for IL-34, specificity of IL-17A (96%) higher than IL-34 (64%), in contrast, IL-34 demonstrating a good sensitivity (78%) than IL-17A (32%), suggesting its potential as a more valuable biomarker for early detection and monitoring of DFU.
The AA genotype of IL-17A gene polymorphism was more frequent among patients (25.7%) compared to controls (8.6%). Similarly, the A allele was more prevalent in patients (28) than in control (15), while the G allele was more prevalent in control (55) than in patients (42), yielding a statistically significant result (P = 0.0187).
These findings suggest that elevated IL-17A and IL-34 serum levels, along with the presence of the IL-17A rs2275913 gene polymorphism, may be associated with increased susceptibility to diabetic foot ulcers. IL-34 may serve as potential biomarker for diagnosis of DFU patients. Moreover, the AA genotype and A allele of the IL-17A gene polymorphism may act as possibility risk factors for diabetic foot ulcer (DFU).