Molecular and geographical heterogeneity of hemoglobinopathy mutations in Azerbaijanian populations

With the carrier rate of 4%-8.6%, β-thalassemia is one of the most prevalent hereditary disorders in Azerbaijan. Taking into consideration the high frequency of β-thalassemia as well as the occurrences of several other hemoglobinopathies, we conducted a large genotyping study to investigate the mutational background of common hemoglobinopathies in the country. Α- and β-globin genes were evaluated in the carriers of mutations identified via hematological indices and hemoglobin fractions (n = 1,757). Genotyping of β-thalassemia carriers identified through population screening revealed 32 mutations, with codon 8 [-AA]-34.96%, IVS-II-1 [G > A]-16.35%, and IVS-I-110 [G > A]-10.12% leading the spectrum. Analysis of associations of β-thalassemia mutations with geographical regions of the country identified the strongest association between codon 8 [-AA] and Shaki-Zaqatala, and codon 5 [-CT] in Mountainous Shirvan regions (ri > 6.00; p < 0.05). HbS, HbD-Punjab, and HbE were the most prevalent among our variant hemoglobin cohort, commonly inherited in compounds with β-thalassemia than in the homozygous state. We identified nine α-thalassemia mutations, 20.5 kb and 3.7 kb deletions together accounting for 74% of the spectrum. Point mutations of α-thalassemia were less common among our observations and were mainly inherited in compounds with deletions. Our results allow a better understanding of the wide spectrum of mutations in Azerbaijan and highlights the high heterogeneity of hemoglobinopathies in the local population.