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Polymorphic mi RNA ‐mediated gene contribution to inhibitor development in haemophilia A
Author(s) -
Bafunno V.,
Santacroce R.,
Chetta M.,
Peyvandi F.,
Sessa F.,
Chinni E.,
Longo V.,
Margaglione M.
Publication year - 2012
Publication title -
haemophilia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.213
H-Index - 92
eISSN - 1365-2516
pISSN - 1351-8216
DOI - 10.1111/j.1365-2516.2012.02882.x
Subject(s) - single nucleotide polymorphism , haemophilia a , microrna , haemophilia , snp , gene , genetics , medicine , biology , bioinformatics , genotype
Summary Development of inhibitory antibodies is perhaps the most serious complication of FVIII replacement therapy, precluding efficient clinical management of patients with haemophilia A ( HA ). The development and function of immune system are also regulated by micro RNA s (mi RNA s). Mutations and changes in the level of expression of some mi RNA genes have been associated with the onset and progression of immunological disorders. The aim of this study was to investigate new genetic polymorphisms in loci for mi RNA and their targets to evaluate whether these SNP s may confer susceptibility to inhibitor development in patients with HA . Italian HA patients with and without inhibitors and healthy controls were recruited in this study. For SNP analysis, standard DNA sequencing method was used. We have studied four SNP s, i.e. rs36101366, rs34683807, rs1803603 and rs3024496 located in the 3′ UTR of F8 and IL ‐10 genes. These SNP s have been checked for their frequencies in patients with and without inhibitors, but no statistically significant differences were found. Then, we have searched for other genetic variants in loci for haematopoietic‐specific mi RNA s, i.e. hsa‐mir‐150 , hsa‐mir‐155 , hsa‐mir‐146a, hsa‐mir‐142, hsa‐mir‐181a and in a specific mi RNA , hsa‐mir‐1184 , i.e. predicted to be located in the intron 22 of F8 gene. For all mi RNA s selected, we did not identify any sequence variation in our study population. This is the first study to demonstrate that there was no association between selected SNP s in mi RNA s and their targets and the susceptibility to inhibitor development in people affected by HA .