PharmGKB summary: heparin-induced thrombocytopenia pathway, adverse drug reaction

Miller, Elise; Norwood, Charles; Giles, Jason B.; Huddart, Rachel; Karnes, Jason H.; Whirl‐Carrillo, Michelle; Klein, Teri E.

doi:10.1097/fpc.0000000000000465

Cited by 1 publication

(2 citation statements)

References 69 publications

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“…Previous studies have demonstrated that heparin-induced thrombocytopenia and adverse drug reaction pathways were associated with UBASH3B gene. 35,36 The sole member of the T-cell ubiquitin ligand (TULA) family among the protein tyrosine phosphatases found in the platelets of both mice and humans is TULA-2. 37 This gene encodes this protein.…”

Section: Discussionmentioning

confidence: 99%

“…These proteins encoded by this gene have the functions of preventing platelet‐derived growth factor receptor and epidermal growth factor receptor from being endocytosed. Previous studies have demonstrated that heparin‐induced thrombocytopenia and adverse drug reaction pathways were associated with UBASH3B gene 35,36 . The sole member of the T‐cell ubiquitin ligand (TULA) family among the protein tyrosine phosphatases found in the platelets of both mice and humans is TULA‐2 37 .…”

Section: Discussionmentioning

confidence: 99%

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Genetic variations in relation to bleeding and pharmacodynamics of dabigatran in Chinese patients with nonvalvular atrial fibrillation: A nationwide multicentre prospective cohort study

Xiang

Xie

Liu

et al. 2022

Clinical & Translational Med

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Introduction To identify the potential factors responsible for the individual variability of dabigatran, we investigated the genetic variations associated with clinical outcomes and pharmacodynamics (PD) in Chinese patients with nonvalvular atrial fibrillation (NVAF). Materials and methods Chinese patients with NVAF taking dabigatran etexilate with therapeutic doses were enrolled. The primary (bleeding events) and secondary (thromboembolic and major adverse cardiac events) outcomes for a 2‐year follow‐up were evaluated. Peak and trough PD parameters (anti‐FIIa activity, activated partial thromboplastin time and prothrombin time) were detected. Whole‐exome sequencing, genome‐wide sequencing and candidate gene association analyses were performed. Results There were 170 patients with NVAF treated with dabigatran (110 mg twice daily) who were finally included. Two single‐nucleotide polymorphisms (SNPs) were significantly related with bleeding, which include UBASH3B rs2276408 (odds ratio [OR] = 8.79, 95% confidence interval [CI]: 2.99–25.83, p = 7.77 × 10−5 at sixth month visit) and FBN2 rs3805625 (OR = 8.29, 95% CI: 2.87–23.89, p = 9.08 × 10−5 at 12th month visit), as well as with increased trends at other visits (p < .05). Furthermore, minor allele carriers of 16 new SNPs increased PD levels, and those of one new SNP decreased PD values (p < 1.0 × 10−5). Lastly, 33 new SNPs were found to be associated with bleeding and PD among 14 candidate genes. Unfortunately, the low number of secondary outcomes precluded further association analyses. Conclusions Genetic variations indeed affected bleeding and PD in Chinese patients with NVAF treated with dabigatran. The functions of these suggestive genes and SNPs might further be explored and verified in more in vivo and in vitro investigations.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%