Analysis of long non-coding RNA expression in hemophilia A patients.

Objectives: Hemophilia A (HA) is an inherited and rare X-linked bleeding disorder which is caused by mutations of the factor VIII gene (FVIII). Long non-coding RNAs (lncRNAs) are non-protein coding sequence transcripts containing more than 200 nucleotides and have potential in diagnosis, prevention and treatment of cancers and inherited bleeding disorders like thalassemia. The goal of this study was to determine the relationship between the expression of lncRNAs and the incidence of hemophilia A in Iranian population.

Methods: In this study, after bioinformatics analysis and lncRNA identification, the expression of two lncRNAs including NONHSAT139215 and NONHSAT139219 was investigated among the blood samples of severe hemophilia A and healthy (non-hemophilia) subjects using the relative qRT-PCR technique.

Results: The melting curve analysis confirmed the specificity of primers. Also, the standard curve showed that the efficiency of reactions for β2-microglobulin (B2M), NONHSAT139215 and NONHSAT139219 was 1.91, 1.96 and 2.01, respectively. On the other hand, the statistical analysis using REST software indicated that the expression of NONHSAT139219 and NONHSAT139215 in severe HA patients was significantly down-regulated as compared to control group (p < .05).

Discussion: Our results demonstrated that a decrease in the expression of two lncRNAs located in FVIII gene may play an important role for the development of severe hemophilia A for the first time.

Conclusions: Briefly, the abnormal expression levels of lncRNAs in hemophilia A cases may be correlated with disease intensity. However, further studies of these lncRNAs are required to provide a useful insight into hemophilia biology.