Association of Interleukin-1 Receptor Antagonist (IL-1RA) Gene Polymorphism with Community-Acquired Pneumonia in North Indian Children: A Case-Control Study

Abstract

Background Community-acquired pneumonia (CAP) is the leading cause of death in children < 5 years of age. The primary objective of the study was to assess the association of IL-1RA gene polymorphism in children aged 2 to 59 months with CAP and the secondary objective was to assess the association of gene polymorphism with mortality among hospitalized CAP cases.
Study Design This case-control study was conducted in a tertiary teaching institute in Northern India. Hospitalized children aged 2 to 59 months with World Health Organization-defined CAP were included as cases after parental consent. Age-matched healthy controls were recruited from the immunization clinic of the hospital. Genotyping was done using polymerase chain reaction to analyze the variable number of tandem repeats of IL-1RA gene polymorphism.
Result From October 2019 to October 2021, 330 cases (123, 37.27% female), and 330 controls (151, 45.75% female) were recruited. Genotype A2/A2 of the IL-1RA gene was found to be associated with the increased risk for CAP children with adjusted odds ratio (AOR) of 12.24 (95% confidence interval [CI] 5.21-28.7, p < 0.001). A2 and A4 alleles were also found to be at risk for CAP. A1/A2 genotype was found to be protective for CAP with an AOR of 0.29 (95% CI 0.19-19.0.45). The genotype A2/A2 and A2 allele of IL-1RA gene was associated with child mortality with CAP cases.
Conclusion In IL1RA gene, A2/A2 genotype and A2 allele were associated with increased risk of CAP and A1/A2 were found to be protective for CAP. The genotype A2/A2 and A2 was associated with CAP mortality.

Keywords

community-acquired pneumonia / interleukin-1 receptor antagonist / variable number of tandem repeats / polymerase chain reaction / odds ratio / adjusted odds ratio

Ethical Approval

The study was approved by the Institutional Ethics Committee of King George's Medical University, Lucknow vide letter no 98th ECM II B-Ph.D/PI dated September 6, 2019.

Consent to Participate

The caregivers/guardians of children signed the written informed consent for participation in this study.

Consent for Publication

All authors have read and agreed to the published version of the manuscript.

Data Availability

All the relevant data are present in the manuscript. The corresponding author has full control of all data and the data may be made available on request.

Code Availability

Not applicable.

Authors' Contributions

Conceptualization, S.A. and N.V.; Methodology, S.A. and N.V.; Investigation, S.A. and N.V.; Resourses, S.A. and P.G.; Data curation, N.V. and A.K.P.; Writing-original draft preparation, S.A. and N.V.; Writing - review and editing, S.A., N.V., and A.K.P.; Supervision, S.A.; Project administration, S.A. All authors have read and agreed to the published version of the manuscript.

Funding

None.

Conflict of Interest

The author(s) declare that there is no conflict of interest.

Acknowledgments

Authors are highly grateful to the participants for their time and valuable contribution in this research. We are also acknowledging the conducive environment provided by the administration of King George's Medical University, Lucknow, Uttar Pradesh, India, which facilitated implementation of this study. We also acknowledge the contribution of Dr. Nidhi Awasthi, for her contribution in this study.

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