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Influence of tissue factor polymorphisms (603A>G and 5466A>G) on plasma tissue factor levels and their impact on deep vein thrombosis risk in young Indian population

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Abstract

Deep vein thrombosis (DVT) is multifactorial disorder and well known to cause substantial morbidity and mortality. There is sparse data in the Asian population, particularly India regarding association of tissue factor (TF) gene single nucleotide polymorphisms (SNPs) with plasma TF levels in DVT. So, we analyzed the distribution of SNPs (603A>G and 5466A>G) in India, to evaluate their effect on TF levels in DVT patients. Plasma level and SNPs (603A>G and 5466A>G) of TF gene were screened in subjects (100 DVT patients and 100 controls). Patients had significantly higher TF levels than controls (patients: 84.95 ± 17.16 pg/ml, controls: 70.55 ± 15.87 pg/ml, p < 0.001). G allele of 603A>G polymorphism was significantly higher in patients than controls (patients: 40.5% controls: 27.5%, p = 0.004). Subjects with AG and GG genotype had significantly higher TF levels than AA genotype (p = 0.001). After multiple logistic regression analysis, risk of DVT was increased 1.398 fold (95% CI 0.738–2.651) and 4.41 fold (95% CI 1.404–13.884) with AG and GG genotype respectively. Allelic and genotypic frequencies of 5466A>G polymorphism was neither associated with TF levels nor with DVT. We found high TF level in patients with TF 603A>G polymorphism, which is an important predisposing factor in increasing risk of DVT in young Indians. Furthermore, GG genotype of 603A>G polymorphism augments the risk of thrombosis by 4.4 fold, thus highlighting the significance of this polymorphism in the development of DVT. So, we suggest that inclusion of 603A>G polymorphism in prothrombotic work-up may be helpful in making the treatment strategy in DVT patients.

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Acknowledgements

We would like to thank the research and technical staff of All India Institute of Medical Sciences (AIIMS), New Delhi for their assistance and support.

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Authors and Affiliations

  1. Department of Hematology, All India Institute of Medical Sciences, New Delhi, 110029, India

    Kamal Kishor, Amit Sharma, Kanwaljeet Singh, Ravi Ranjan, Hareram Pandey, Ravi Kumar, Pravas Mishra, Manoranjan Mahapatra & Renu Saxena

  2. Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, 110029, India

    Vineet Kumar Kamal

  3. Department of Hematology, AIIMS, Room Number-205, IInd Floor New Private Ward, New Delhi, 110029, India

    Renu Saxena

Authors
  1. Kamal Kishor
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  2. Amit Sharma
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  6. Ravi Kumar
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  10. Renu Saxena
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Contributions

KK designed the study, performed experimental studies and drafted the manuscript. AS compiled the data, performed analysis and contributed to writing. KS and RR helped in drafting the manuscript. HP and RK reviewed the manuscript and helped in shaping the manuscript. VKK performed statistical analysis and interpretation of data. PM, MM and RS provided valuation suggestions and clinical inputs. All the authors read and approved the final manuscript.

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Correspondence to Renu Saxena.

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The authors declared that they have no conflict of interest.

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The Institutional Ethics Committee of AIIMS approved this study.

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Written informed consent was obtained from all the participants.

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Kishor, K., Sharma, A., Singh, K. et al. Influence of tissue factor polymorphisms (603A>G and 5466A>G) on plasma tissue factor levels and their impact on deep vein thrombosis risk in young Indian population. J Thromb Thrombolysis 46, 88–94 (2018). https://doi.org/10.1007/s11239-018-1666-6

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  • DOI: https://doi.org/10.1007/s11239-018-1666-6

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