Presentation Details
| The p.D1472H polymorphism in the VWF gene is common in Indian patients Ritika Sharma, Manu Jamwal, Harikishen Senee, Narender Kumar, Arihant Jain, Pankaj Malhotra, Deepak Bansal, Reena Das, Jasmina Ahluwalia. Postgraduate Institute of Medical Education and Research, Chandigarh, India |
Abstract
Introduction: The p.D1472H polymorphism in the VWF gene may affect the measurement of activity levels by the VWF GPIbR assays and lead to abnormal activity to antigen ratios .This may impact the diagnosis of VWD. Population studies have shown this polymorphism to be commoner in some races. There is currently a paucity of information on the prevalence of this mutation in the Indian population and patients with bleeding. Methods: Patients with a bleeding defect due to deficiencies in Factor II, V, VII, X, XIII, fibrinogen, VWF and platelet functions as suggested by preliminary coagulation screens, relevant factor assays, light transmission aggregometry or flow cytometry were subjected to targeted NGS resequencing. Patients of Hemophilia A who were negative for common inversion 22 and intron 1 and cases of Hemophilia B where Sanger sequencing initially failed to reveal a mutation were included. The VWF Ag and VWF GPIbR levels were assayed from plasma samples on the ACL TOP 500 Coagulation analyser using the LIA kits.Targeted next generation resequencing was done using a 66 gene panel on the Illumina Miseq platform. Cases of hemolytic anemia undergoing resequencing to diagnose the cause of anemia were included as non-disease controls. Results: Three hundred and seven cases with a likely bleeding disorder and 72 with anemia and no bleeding (non disease controls) were screened. The positivity in cases was not significantly different from controls (66 i.e. 21% vs 21 i.e. 29%, p =1.5). The 6 homozygous cases comprised 4 cases with severe VWD and 2 with FVII deficiency. No controls were homozygous. In the heterozygous group (60), the mean VWF antigen and GPIbR values varied significantly among those with and without VWD; however, the GPIbR: VWF Ag ratios did not (p=0.27).The polymorphism was seen in 3 cases of severe and 1 each of Type 2, 2B and acquired Von Willebrand syndrome and 2 cases of low VWF (with no mutation in the VWF gene). Among the bleeding disorders, 21.3, 24, 17,40, 26,29 and 18.5% of cases with deficiency in VWF /FVII/FVIII / FIX/FXIII /rare coagulation factors or a platelet function defect, respectively, were positive for the polymorphism. Conclusions: The p.D1472H polymorphism is frequent in the Indian population. Homozygosity is rare. The positivity across various coagulation factor deficiencies is comparable. The VWF GpIbR activity / VWF antigen ratio may not help to distinguish between individuals with or without the polymorphism.
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No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.