New associations: INFG and TGFB1 genes and the inhibitor development in severe haemophilia A. (30th April 2015)

• Record Type: Journal Article
• Authors: de Alencar, J. B.; Macedo, L. C.; de Barros, M. F.; Rodrigues, C.; Shinzato, A. H.; Pelissari, C. B.; Machado, J.; Sell, A. M.; Visentainer, J. E. L.
• Is Part Of: Haemophilia. Volume 21:Number 4(2015:Jul.)
• Page Start: e312
• Page End: e316
• Publication Date: 2015-04-30
• Subjects: Hemophilia -- Periodicals; 616.1572005
• DOI: 10.1111/hae.12685
• Languages: English
• ISSNs: 1351-8216

Abstract

<abstract abstract-type="main" id="hae12684-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="hae12685-sec-0001" sec-type="section"> <title>Introduction</title> <p>The development of factor VIII (FVIII) inhibitor is the main complication of replacement therapy in patients with haemophilia A (HA). A ratio of 5–7% of individuals HA develops antibodies (inhibitors) against the FVIII infused during the treatment, thereby reducing their pro‐coagulant activity. The immunomodulatory cytokine genes have been related to the risk of development of alloantibodies in several studies, mainly in HA with severe form.</p> </sec> <sec id="hae12685-sec-0002" sec-type="section"> <title>Aim</title> <p>We investigated the polymorphisms in regulatory regions of cytokine genes (<italic>IL1A</italic>, <italic> IL1B</italic>, <italic> IL1R</italic>, <italic> IL1RA</italic>, <italic> IL4RA, IL12</italic>, <italic> INFG, TGFB1, TNF</italic>, <italic> IL2</italic>, <italic> IL4</italic>, <italic> IL6, IL10)</italic> that could influence the risk of developing inhibitors in patients with severe HA.</p> </sec> <sec id="hae12685-sec-0003" sec-type="section"> <title>Methods</title> <p>The genotyping of cytokine genes of 117 patients with HA was performed by polymerase chain reaction with sequence‐specific primers (PCR‐SSP) using the protocol recommended by the manufacturer (Invitrogen kit Cytokines<sup>®</sup>, Canoga Park, USA)</p> </sec> <sec id="hae12685-sec-0004" sec-type="section"> <title>Results</title> <p>From the cohort of 117 patients with severe HA, 35 developed inhibitors. There was a higher frequency of +874 T allele in <italic>INFG</italic> and of +869 TT and TG/TG in <italic>TGFB1</italic> genes on patients with inhibitors.</p> </sec> <sec id="hae12685-sec-0005" sec-type="section"> <title>Conclusion</title> <p>This suggests that polymorphisms in <italic>INFG</italic> and in <italic>TGFB1</italic> genes are related to risk of developing inhibitor, and could contribute to a genetic profile of the individual HA for the risk of inhibitors development to FVIII.</p> </sec> </abstract>