title: The beta 1 tubulin R307H single nucleotide polymorphism is associated with treatment failures in immune thrombocytopenia (ITP).
abstract: 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.
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA. pab7003@med.cornell.edu
authors.forename: Paul A
authors.initials: PA
authors.lastname: Basciano
authors.forename: James
authors.initials: J
authors.lastname: Bussel
authors.forename: Zeeshan
authors.initials: Z
authors.lastname: Hafeez
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Christos
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Giannakakou
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D001565:Benzoates / Q000627:therapeutic use; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006834:Hydrazines / Q000627:therapeutic use; D007155:Immunologic Factors / Q000627:therapeutic use*; D007223:Infant; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010976:Platelet Count; D020641:Polymorphism, Single Nucleotide; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D011720:Pyrazoles / Q000627:therapeutic use; D011961:Receptors, Fc / Q000627:therapeutic use; D053628:Receptors, Thrombopoietin / Q000819:agonists*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D000069283:Rituximab; D013844:Thiazoles / Q000627:therapeutic use; D013876:Thiophenes / Q000627:therapeutic use; D034061:Thrombopoiesis / Q000235:genetics; D013926:Thrombopoietin / Q000627:therapeutic use; D017211:Treatment Failure; D014404:Tubulin / Q000235:genetics*
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D001565:Benzoates; D015415:Biomarkers; D006834:Hydrazines; D007155:Immunologic Factors; D011720:Pyrazoles; D011961:Receptors, Fc; D053628:Receptors, Thrombopoietin; D011993:Recombinant Fusion Proteins; C578986:TUBB1 protein, human; D013844:Thiazoles; D013876:Thiophenes; D014404:Tubulin; C082218:MPL protein, human; C533238:avatrombopag; D000069283:Rituximab; D013926:Thrombopoietin; C488777:romiplostim; C520809:eltrombopag