Gender-specific transcriptional profiles identified in β-thalassemia patients

ABSTRACT: Lifelong treatment and major complications characterize β-thalassemia patients, whether they suffer from the milder type of the disease (β-thalassemia intermedia, TI) or the severe type (β-thalassemia major, TM). This study aimed to ascertain the differences in the transcriptional profiles of TI and TM patients to identify targets for stratification and the development of personalized therapeutic strategies. RNA-seq of 49 participants (16 TI, 16 TM, 17 healthy) identified a higher number of differentially expressed genes in TM than in TI patients when compared to healthy participants portraying accurately the clinical observations. When TI patients were compared to TM, the absence of significantly differentially expressed genes highlighted the increased variability seen in the TI expression profiles suggesting that a continuous spectrum describes the disease and not distinct conditions. Although no confounding effect was seen due to different centers, age groups and various clinical characteristics, when male and female patients were compared to healthy participants of the same gender, it was evident that males and females are affected in distinctive ways by β-thalassemia. TI triggers a pronounced and consistent transcriptional signature in males, whereas a small effect is seen in females reflecting increased biological variability. TM induces transcriptional changes of similar magnitude in both genders with limited overlap between them emphasizing that different pathways are affected. Our study provides a framework for further stratification studies in β-thalassemia and highlights the need to consider gender as an important variable for developing differential diagnostic and therapeutic strategies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE117221 | GEO | 2020/08/25

REPOSITORIES: GEO