MTHFR C677T polymorphism and T2DM risk in Iraqi Kurds: a cross-sectional study

Type 2 diabetes mellitus (T2DM) represents a major global health problem, and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism has been repeatedly linked to T2DM susceptibility. However, no prior study has investigated this association in the Iraqi Kurdish population. This study aimed to examine the relationship between the MTHFR C677T polymorphism and T2DM in a sample of Iraqi Kurdish patients, and to evaluate its effects on metabolic parameters, lipid profiles, and the incidence of diabetic complications.

Diabetic Center in Azadi Teaching Hospital - from various districts of the Duhok Governorate - at the Duhok Blood Bank. - The study protocol was approved by the General Directorate of Health Ethics Committee, Duhok, Kurdistan Region, Iraq (protocol code: 29052024-4-5; approval date: 29 March 2024).

Of the Duhok Diabetic Center.

Blood samples were obtained at the Duhok Diabetic Center in Azadi Teaching Hospital and subsequently transported to the Duhok Central Laboratory for genetic analysis.

From the Duhok Governorate.

Compared with controls, T2DM patients had higher blood pressure (BP), waist circumference (WC), body mass index (BMI), and glycated hemoglobin (HbA1c) (P < 0.001). The CT genotype frequency was 38.57% in T2DM vs. 16.42% in controls (OR = 4.45, 95% CI: 2.49-7.97), and the TT genotype frequency was 20.00% in T2DM vs. 5.00% in controls (OR = 7.59, 95% CI: 3.12-18.42). The TT genotype was associated with lower high-density lipoprotein cholesterol (HDL-C) (42.37 ± 6.68 mg/dL; P < 0.001) and higher homocysteine (Hcy) levels (22.08 ± 5.74 µmol/L). T2DM patients also had elevated albumin-to-creatinine ratio (ACR) (190.80 ± 214.84 mg/g creatinine) and reduced estimated glomerular filtration rate (eGFR) (86.91 ± 22.19 mL/min/1.73 m²) (both P < 0.001), especially in the TT genotype group.

The MTHFR C677T polymorphism is strongly associated with T2DM in Iraqi Kurdish patients, with the T allele linked to adverse metabolic profiles and a higher risk of complications. These findings highlight the potential clinical value of incorporating genetic screening into early risk assessment and personalized management strategies in high-risk populations.