Publication Only: Thalassemias
Azerbaijan is located in Transcaucasia, which is a high prevalent region of hemoglobinopathies. Besides β-thalassemia, the local population is also known for the presence of α-thalassemia and some hemoglobin variants. Several previous studies reported the incidences of α-thalassemia and hemoglobin variants such as HbS, HbE and HbD, as well as incidence rate and mutation spectrum of β-thalassemia in the local population. Nevertheless, these were mainly conducted in small study groups and they were limited on β-globin genotyping, which necessitated a large-scale screening and genotyping to reveal phenotypes and mutational background of all common hemoglobinopathies in Azerbaijan.
The aim of our study was to screen a large sample of population in order to reveal the prevalence of thalassemias and variant hemoglobins as well as their mutational background in Azerbaijan.
The sample group included 436,144 individuals (population = 9,982,952) applying for marriage certificate, which were screened via Thalassemia Prevention Program of Azerbaijan. Premarital screening of thalassemia is mandatory since 2015, covering almost all areas of the country. Total hemoglobin (Hb) levels, red blood cell indices and Hb pattern analysis were evaluated in all samples. Genotyping of selected samples were performed via reverse dot blot hybridization and sequencing techniques.
The screening of more than 4% of the population revealed following carrier frequencies of hemoglobinopathies: α-thalassemia - 10.1%, β-thalassemia - 3.71%, HbS - 0.082%, HbC - 0.382%, HbE - 0.087% and HbD Punjab - 0.068%. The frequency of α-thalassemia was calculated via Hardy-Weinberg equation, based on the count of individuals with HbH. Genotyping of the carriers revealed 33 β-thalassemia and 9 α-thalassemia mutations. The most common β-thalassemia mutations were frameshifts and mRNA processing mutations accounting for β0 phenotype: Codon 8 [-AA] - 34.7%, IVS-II-1 [G > A] - 16.7%, IVS-I-110 [G > A] - 9.7%, Codon 8/9 [+G] - 4.8%, and Codon 36/37 [-T] - 4.3% (N = 1252). The most prevalent α-thalassemia mutations, on the other hand, were deletions accounting for milder phenotype of HbH disease: 20.5 kb DEL - 43.8% and 3.7 kb DEL - 35.4% (N = 144).
This is the largest study to date evaluating phenotypic and genotypic diversity of hemoglobinopathies in Azerbaijan, and we hereby provided the first report on carrier frequencies of hemoglobin variants in the country. The screening and genotyping results revealed that hemoglobinopathies are highly heterogenous in Azerbaijan. β-Thalassemia, although accounts for a lower frequency comparing to α-thalassemia, is associated with severe phenotypes, including the possibility of coinheritance with clinically significant variants as HbS and HbE.