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

Neha Verma, Shally Awasthi, Anuj K. Pandey, Prashant Gupta

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Global Medical Genetics ›› 2023, Vol. 10 ›› Issue (02) : 109-116. DOI: 10.1055/s-0043-1770056
Original Research Article
Original Research Article

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

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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

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Neha Verma, Shally Awasthi, Anuj K. Pandey, Prashant Gupta. Association of Interleukin-1 Receptor Antagonist (IL-1RA) Gene Polymorphism with Community-Acquired Pneumonia in North Indian Children: A Case-Control Study. Global Medical Genetics, 2023, 10(02): 109‒116 https://doi.org/10.1055/s-0043-1770056

References

[1]
World Health Organization (WHO a). 2021 Accessed July 2, 2022 at: https://www.who.int/news-room/fact-sheets/detail/pneumonia
[2]
Patwari PP, O'Cain P, Goodman DM. et al. Interleukin-1 receptor antagonist intron 2 variable number of tandem repeats polymorphism and respiratory failure in children with community-acquired pneumonia. Pediatr Crit Care Med 2008; 9(06) 553-559
[3]
Awasthi S, Yadav KK, Pandey M, Mahdi AA, Awasthi N.Interleukin 1 receptor antagonist (IL1RA) gene polymorphism and levels associated with adverse outcome in severe community-acquired pneumonia in children: a hospital-based study in India. Pediatr Pulmonol 2018; 53(09) 1276-1283
[4]
Santtila S, Savinainen K, Hurme M.Presence of the IL-1RA allele 2 (IL1RN*2) is associated with enhanced IL-1beta production in vitro. Scand J Immunol 1998; 47(03) 195-198
[5]
Wardlaw T, Johanssan EW, Hodge M.Pneumonia: the forgotten killer of children. UNICEF and WHO. 2006. Accessed May 26, 2016 at: http://apps.who.int/iris/bitstream/10665/43640/1/9280640489_eng.pdf
[6]
Duke T, Subhi R, Peel D, Frey B.Pulse oximetry: technology to reduce child mortality in developing countries. Ann Trop Paediatr 2009; 29(03) 165-175
[7]
Bhat RY, Manjunath N.Correlates of acute lower respiratory tract infections in children under 5 years of age in India. Int J Tuberc Lung Dis 2013; 17(03) 418-422
[8]
Nemani T, Awasthi S.Malnutrition and anaemia associated with hypoxia among hospitalised children with community-acquired pneumonia in North India. Clin Epidemiol Glob Health 2016; 4: 17-21
[9]
Dinarello CA.Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood 2011; 117(14) 3720-3732
[10]
Blakemore AI, Tarlow JK, Cork MJ, Gordon C, Emery P, Duff GW.Interleukin-1 receptor antagonist gene polymorphism as a disease severity factor in systemic lupus erythematosus. Arthritis Rheum 1994; 37(09) 1380-1385
[11]
Bioque G, Crusius JB, Koutroubakis I.et al.Allelic polymorphism in IL-1 β and IL-1 receptor antagonist (IL-1Ra) genes in inflammatory bowel disease. Clin Exp Immunol 1995; 102(02) 379-383
[12]
Tarlow JK, Clay FE, Cork MJ.et al.Severity of alopecia areata is associated with a polymorphism in the interleukin-1 receptor antagonist gene. J Invest Dermatol 1994; 103(03) 387-390
[13]
Li H, Wu Y, Zhao R.et al.IL-1RN gene polymorphisms reduces thyroid cancer risk in Chinese Han population. Mol Carcinog 2020; 59(10) 1140-1146
[14]
Revised WHO classification and treatment of childhood pneumonia at health facilities. Accessed July 25, 2022 at: https://apps.who.int/iris/bitstream/handle/10665/137319/9789241507813_eng.pdf
[15]
Standardisation of Interpretation of Chest Radiographs for the Diagnosis of Pneumonia in Children. Geneva: WHO; 2001. Accessed January 23, 2016 at: http://apps.who.int/iris/bitstream/10665/66956/1/WHO_V_and_B_01.35.pdf
[16]
Heffner JE, Klein JS, Hampson C.Interventional management of pleural infections. Chest 2009; 136(04) 1148-1159
[17]
Sharma R.Revised Kuppuswamy's socioeconomic status scale: explained and updated. Indian Pediatr 2017; 54(10) 867-870
[18]
World Health Organization (WHO). Management of severe malnutrition: a manual for physicians and other senior health workers. World Health Organization; 1999. WHO Classification for Malnutrition. Available at: https://www.who.int/publications/i/item/9241545119
[19]
Bid HK, Kumar A, Mishra PK, Mittal RD.Study of interleukin-1 receptor antagonist (IL-1Ra) gene polymorphism in healthy individuals from Northern India. Indian J Clin Biochem 2004; 19(02) 119-123
[20]
Tarlow JK, Blakemore AI, Lennard A.et al.Polymorphism in human IL-1 receptor antagonist gene intron 2 is caused by variable numbers of an 86-bp tandem repeat. Hum Genet 1993; 91(04) 403-404
[21]
Arnalich F, López-Maderuelo D, Codoceo R.et al.Interleukin-1 receptor antagonist gene polymorphism and mortality in patients with severe sepsis. Clin Exp Immunol 2002; 127(02) 331-336
[22]
Rider LG, Artlett CM, Foster CB.et al; Childhood Myositis Heterogeneity Collaborative Study Group. Polymorphisms in the IL-1 receptor antagonist gene VNTR are possible risk factors for juvenile idiopathic inflammatory myopathies. Clin Exp Immunol 2000; 121(01) 47-52
[23]
Huet T, Beaussier H, Voisin O.et al.Anakinra for severe forms of COVID-19: a cohort study. Lancet Rheumatol 2020; 2(07) e393-e400
[24]
FDA Letter of Authorization (LOA). Kineret LOA 11082022.Available at: https://www.fda.gov/media/163081/download

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