The beta 1 tubulin R307H single nucleotide polymorphism is associated with treatment failures in immune thrombocytopenia (ITP)

Authors

  • Paul A. Basciano,

    Corresponding author
    • Division of Hematology and Oncology, Department of Medicine, Weill Cornell Medical College, New York, NY, USA
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  • James Bussel,

    1. Division of Hematology and Oncology, Department of Medicine, Weill Cornell Medical College, New York, NY, USA
    2. Platelet Disorders Center, Department of Pediatrics, Weill Cornell Medical College, New York, NY, USA
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  • Zeeshan Hafeez,

    1. Platelet Disorders Center, Department of Pediatrics, Weill Cornell Medical College, New York, NY, USA
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  • Paul J. Christos,

    1. Division of Biostatistics and Epidemiology, Department of Public Health, Weill Cornell Medical College, New York, NY, USA
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  • Paraskevi Giannakakou

    1. Division of Hematology and Oncology, Department of Medicine, Weill Cornell Medical College, New York, NY, USA
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Correspondence: Paul A. Basciano, Division of Hematology and Oncology, Department of Medicine, Weill Cornell Medical College, 1300 York Avenue C-610C, New York 10065-4896, NY, USA.

E-mail: pab7003@med.cornell.edu

Summary

Predictive biomarkers are needed in immune thrombocytopenia (ITP). Single nucleotide polymorphisms (SNPs) in beta 1 tubulin are potential candidates, as beta 1 tubulin is integral for platelet production and function, and SNPs in beta 1 tubulin have been associated with distinct phenotypes in platelets. We investigated the most prevalent beta 1 tubulin SNP (R307H) as a biomarker in patients with ITP via a retrospective chart review. Allelic frequencies between a group of 191 ITP patients and a healthy control group showed no difference, suggesting no direct aetiological role for the SNP in ITP. However, over similar periods of follow-up, both heterozygote and homozygote minor allele ITP patients were treated with significantly more treatment modalities and had significantly higher risk of failure to immune-modulatory therapies [relative risk (RR) = 1·5, 95% confidence interval (CI) = 1·1–2·1; P = 0·01]; with rituximab, in particular, ITP patients with the SNP experienced a 58% failure rate (RR = 1·6, 95%CI = 1·03–2·5; P = 0·04). Analysis of the absolute immature platelet fraction (A-IPF) as a marker of platelet production showed that SNP patients had significantly higher median A-IPFs compared to non-SNP patients when complete responses were achieved using immune modulatory therapies. The data suggest that the beta 1 tubulin R307H SNP has potential for use as a biomarker in ITP and may affect platelet turnover.

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