Association of NRAMP1 (rs3731864) gene polymorphism with hepcidin, D-dimer, and thrombin levels in Iraqi patients with type 2 diabetes mellitus

Abstract

Background & objective: Type 2 Diabetes Mellitus (T2DM) is a multifactorial disorder, in which genetic susceptibility and dysregulation of iron metabolism and coagulation play significant roles. The NRAMP1 gene (SLC11A1), which is involved in innate immunity and iron homeostasis, is a candidate for influencing T2DM risk, although populationspecific data are limited. We study aimed to investigate the association between the NRAMP1 rs3731864 polymorphism and hepcidin, D-dimer, and human thrombin levels in Iraqi patients with T2DM.

Methodology: A case-control study was conducted on 120 subjects (60 T2DM patients and 60 healthy controls).
Genotyping of the rs3731864 polymorphism was performed by PCR. Serum hepcidin and thrombin levels were
measured using Enzyme-Linked Fluorescent Assay (ELFA), and plasma D-dimer was quantified with a FineCare™ FIA meter.

Results: The minor A allele of rs3731864 was associated with enhanced risk of T2DM (OR = 0.28, 95%CI: 0.144-0.58, P = 0.0005). T2DM patients had significantly higher circulating D-dimer (P < 0.0001) and thrombin levels (P = 0.0035), but lower hepcidin levels (P = 0.0025) than controls. But the levels of hepcidin were statistically higher in poorcontrolled glycemic (HbA1c ≥7%) patients. Good diagnostic accuracy of hepcidin (0.73) and D-dimer was revealed by analysis of ROC curve (AUC=0.69).

Conclusion: NRAMP1 rs3731864 A allele is a significant risk factor for T2DM in the Iraqi population. This genetic
predisposition is accompanied by a prothrombotic state and altered iron metabolism, highlighting the interplay
between innate immunity, coagulation, and iron regulation in T2DM.

Keywords: Diabetes Mellitus, Type 2; NRAMP1 Protein; Hepcidins; Fibrinogen; Thrombin; Iraq.

Citation: Khwein MA, Jabir FA. Association of NRAMP1 (rs3731864) gene polymorphism with hepcidin, D-dimer, and thrombin levels in Iraqi patients with type 2 diabetes mellitus. Anaesth. pain intensive care 2025;30(2):207-214. DOI: 10.35975/apic.v30i2.3128

Received: December 07, 2025; Revised: January 03, 2026; Accepted: January 03, 2026