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Thyroid Peroxidase and its Gene Variants as Diagnostic Markers in Subclinical Hypothyroidism: Evidence from a Duhok
Larsa Naji Adam1,2, Awat Mustafa Abbas3,4
1Department of Biology, College of Science, University of Zakho, Duhok, Kurdistan Region, Iraq. larsa.adam@visitor.uoz.edu.krd.
Abstract:
Elevated TSH with normal T3 and T4 levels is a sign of subclinical hypothyroidism (SCH), is often linked to autoimmune thyroiditis. Thyroid peroxidase antibodies (anti-TPO) are early markers, but their diagnostic value and genetic associations in Middle Eastern populations are not well understood. This study assessed serum TPO levels and TPO gene polymorphisms in relation to SCH in Duhok, Iraq (September-December 2024). In a case-control design, 78 patients with SCH and 75 age- and gender-matched euthyroid controls were recruited. Serum levels of TSH, T3, T4, Vitamin D, and anti-TPO were measured. Genotyping of the TPO T1936C variant was performed by ARMS-PCR. Two-sided statistical tests were applied. Correlations were assessed using Spearman's ρ, and genotype frequencies were tested for Hardy-Weinberg equilibrium. Diagnostic performance of anti-TPO was evaluated by receiver operating characteristic (ROC) analysis, including area under the curve (AUC), 95% CI, and Youden index. Patients with SCH showed significantly elevated anti-TPO levels compared to controls (107.5 ± 149.6 vs. 39.5 ± 81.6 IU/mL; p = 0.014). ROC analysis identified ≥ 60.4 IU/mL as the optimal anti-TPO cut-off for SCH prediction (AUC = 0.62, 95% CI: 0.52-0.71, sensitivity = 47.44%, specificity = 89.33%). TPO levels correlated positively with TSH (Spearman ρ = 0.174, p = 0.031), but not with T3, T4, or Vitamin D. TPO (T1936C) gene polymorphism analysis revealed no significant association with SCH (AA genotype: 80.77% in cases vs. 77.33% in controls), (GA genotype: 19.23% in cases vs. 22.67% in controls) p = 0.85. The GG genotype was absent in both groups. Anti-TPO antibodies demonstrated high specificity but modest sensitivity as diagnostic markers for SCH. The TPO T1936C variant was not associated with SCH, though this null finding may reflect the study's limited statistical power. These results highlight the role of autoimmune markers in SCH diagnosis within the Kurdish population of Duhok, Iraq.
