Molecular epidemiology and hematological thresholds for αβ-thalassemia: a retrospective cohort study in the Huizhou region of southern China.

Objectives: To investigate the prevalence, hematological characteristics and optimal cutoff values for mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) in carriers with combined α- and β-thalassemia (αβ-thalassemia) in the Huizhou region of southern China.

Methods: The epidemiological investigation, including prevalence assessment and genotype distribution analysis of αβ-thalassemia, was conducted in a cohort of 14,146 participants (Prevalence cohort). Furthermore, a comprehensive comparative analysis of hematological parameters was performed among 13,888 individuals grouped by genotype (Phenotype cohort).

Results: We found a prevalence rate of 0.86% for αβ-thalassemia in the Huizhou region, with 72 genotypes identified, and the predominant genotype was --/αα, β/β (19.16%). Significant differences in MCV and MCH were found between all genotype groups. Compared to pure β-thalassemia carriers, individuals co-inherited with α/αα and α/αα exhibited improved hematological profiles, while individuals co-inherited with α/α displayed more severe phenotype. ROC analysis demonstrated superior diagnostic performance of MCV/MCH in β/β versus β/β carriers. MCV ≤ 56 fL and/or MCH ≤ 17.4 pg strongly indicated α/α, β/β, while MCV ≤ 56.70 fL and/or MCH ≤ 18.30 pg demonstrated robust diagnostic performance for α/α, β/β carriers, and MCV > 66.47 fL and/or MCH > 21.59 pg were strongly suggestive of the presence of α/αα, β/β. Moreover, we found 371 (18.41%) of 2,015 αβ-thalassemia carriers had the same type of thalassemia as their spouses.

Conclusion: This study suggests that particular attention should be paid to αβ-thalassemia during premarital and pre-pregnancy examinations. Our findings provide a comprehensive theoretical foundation for the genetic counseling, prenatal diagnosis, disease control and screening of αβ-thalassemia.