Original Article

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Blood Res 2017; 52(4):

Published online December 31, 2017

https://doi.org/10.5045/br.2017.52.4.264

© The Korean Society of Hematology

Interleukin-1B (IL-1B-31 and IL-1B-511) and interleukin-1 receptor antagonist (IL-1Ra) gene polymorphisms in primary immune thrombocytopenia

Deependra Kumar Yadav1, Anil Kumar Tripathi1*, Divya Gupta2, Saurabh Shukla1, Aloukick Kumar Singh5, Ashutosh Kumar3, Jyotsna Agarwal4, and K. N. Prasad5

1Department of Clinical Hematology, King George's Medical University, Lucknow, India.

2Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.

3Department of Pathology, King George's Medical University, Lucknow, India.

4Department of Microbiology, King George's Medical University, Lucknow, India.

5Department of Microbiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.

Correspondence to : Anil Kumar Tripathi, M.D. Department of Clinical Hematology, King George's Medical University, Lucknow - 226003, India. aktkgmu@gmail.com

Received: December 6, 2016; Revised: May 19, 2017; Accepted: June 29, 2017

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Immune thrombocytopenia (ITP) is an immune-mediated disease caused by autoantibodies against platelets membrane glycoproteins GPIIb/IIIa and GPIb/IX. The etiology of ITP remains unclear. This study evaluated the association of polymorphisms in interleukin (IL)-1B-31, IL-1B-511, and IL-1Ra with ITP.

Methods

Genotyping of IL-1B-31, IL-1B-511, and IL-1Ra was performed in 118 ITP patients and 100 controls by polymerase chain reaction restriction fragment length polymorphism and detection of variable number tandem repeats.

Results

Genotype differences in IL-1B-31 and IL-1Ra were significantly associated with ITP. Patients showed a higher frequency of the IL-1B-31 variant allele (T) and a 1.52-fold greater risk of susceptibility to ITP (odds ratio [OR]=1.52, 95% confidence interval [CI]=1.04?2.22, P=0.034). The frequencies of both homozygous and heterozygous variant genotypes of IL-1B-31 were higher (OR=2.33, 95% CI=1.069?5.09, P=0.033 and OR=2.044, 95% CI=1.068?39, P=0.034) among patients and were significantly associated with ITP susceptibility. Both homozygous and heterozygous variant genotypes of IL-1Ra were also more frequent (OR=4.48, 95% CI=1.17?17.05, P=0.0230 and OR=1.80, 95% CI=1.03?3.14, P=0.0494) among patients and were associated with ITP risk. IL-1B-31 and IL-1Ra also showed significant association with severe ITP. However, IL-1B-511 was not associated with ITP.

Conclusion

IL-1B-31 and IL-1Ra polymorphisms may significantly impact ITP risk, and they could be associated with disease severity, which may contribute to the pathogenesis of ITP.

Keywords Primary immune thrombocytopenia, IL-1B-31, IL-1B-511, IL-1Ra polymorphism, PCR-RFLP

Article

Original Article

Blood Res 2017; 52(4): 264-269

Published online December 31, 2017 https://doi.org/10.5045/br.2017.52.4.264

Copyright © The Korean Society of Hematology.

Interleukin-1B (IL-1B-31 and IL-1B-511) and interleukin-1 receptor antagonist (IL-1Ra) gene polymorphisms in primary immune thrombocytopenia

Deependra Kumar Yadav1, Anil Kumar Tripathi1*, Divya Gupta2, Saurabh Shukla1, Aloukick Kumar Singh5, Ashutosh Kumar3, Jyotsna Agarwal4, and K. N. Prasad5

1Department of Clinical Hematology, King George's Medical University, Lucknow, India.

2Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.

3Department of Pathology, King George's Medical University, Lucknow, India.

4Department of Microbiology, King George's Medical University, Lucknow, India.

5Department of Microbiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.

Correspondence to:Anil Kumar Tripathi, M.D. Department of Clinical Hematology, King George's Medical University, Lucknow - 226003, India. aktkgmu@gmail.com

Received: December 6, 2016; Revised: May 19, 2017; Accepted: June 29, 2017

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Immune thrombocytopenia (ITP) is an immune-mediated disease caused by autoantibodies against platelets membrane glycoproteins GPIIb/IIIa and GPIb/IX. The etiology of ITP remains unclear. This study evaluated the association of polymorphisms in interleukin (IL)-1B-31, IL-1B-511, and IL-1Ra with ITP.

Methods

Genotyping of IL-1B-31, IL-1B-511, and IL-1Ra was performed in 118 ITP patients and 100 controls by polymerase chain reaction restriction fragment length polymorphism and detection of variable number tandem repeats.

Results

Genotype differences in IL-1B-31 and IL-1Ra were significantly associated with ITP. Patients showed a higher frequency of the IL-1B-31 variant allele (T) and a 1.52-fold greater risk of susceptibility to ITP (odds ratio [OR]=1.52, 95% confidence interval [CI]=1.04?2.22, P=0.034). The frequencies of both homozygous and heterozygous variant genotypes of IL-1B-31 were higher (OR=2.33, 95% CI=1.069?5.09, P=0.033 and OR=2.044, 95% CI=1.068?39, P=0.034) among patients and were significantly associated with ITP susceptibility. Both homozygous and heterozygous variant genotypes of IL-1Ra were also more frequent (OR=4.48, 95% CI=1.17?17.05, P=0.0230 and OR=1.80, 95% CI=1.03?3.14, P=0.0494) among patients and were associated with ITP risk. IL-1B-31 and IL-1Ra also showed significant association with severe ITP. However, IL-1B-511 was not associated with ITP.

Conclusion

IL-1B-31 and IL-1Ra polymorphisms may significantly impact ITP risk, and they could be associated with disease severity, which may contribute to the pathogenesis of ITP.

Keywords: Primary immune thrombocytopenia, IL-1B-31, IL-1B-511, IL-1Ra polymorphism, PCR-RFLP

Demographic details of ITP patients and healthy control subjects.
Influence of <italic>IL-1B-31</italic>, <italic>IL-1B-511</italic>, and <italic>IL-1Ra</italic> polymorphisms on susceptibility to ITP and on control subjects.

a)Statistically significant susceptible genotype..

Abbreviations: CI, confidence interval; OR, odds ratio..


Influence of <italic>IL-1B-31</italic>, <italic>IL-1B-511</italic> and <italic>IL-1Ra</italic> polymorphisms on severe, non-severe ITP patients and control subjects.

a)Statistically significant susceptible genotype..

Abbreviations: CI; confidence Interval; OR, odds ratio..


<italic>IL-1B-31</italic>, <italic>IL-1B-511</italic>, and <italic>IL-1Ra</italic> genotype distribution in responder (complete+partial responder) and non-responder.

a)Statistically significant susceptible genotype..

Abbreviations: CI, confidence interval; OR, odds ratio..


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