Increased mortality in the A/A genotype of the SNP rs28372698 of interleukin 32

Alehagen,Urban; Shamoun,Levar; Dimberg,Jan Ingvar; Wågsäter,Dick

doi:10.3892/etm.2020.9559

February-2021 Volume 21 Issue 2

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February-2021 Volume 21 Issue 2

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Article Open Access

Increased mortality in the A/A genotype of the SNP rs28372698 of interleukin 32

Authors:
- Urban Alehagen
- Levar Shamoun
- Jan Ingvar Dimberg
- Dick Wågsäter
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Affiliations: Division of Cardiovascular Medicine, Department of Medicine and Health Sciences, Faculty of Health Sciences, Linköping University, SE‑581 85 Linköping, Sweden, Division of Medical Diagnostics, Department of Laboratory Medicine, Jönköping County, SE‑553 05 Jönköping, Sweden, Department of Natural Science and Biomedicine, School of Health and Welfare, Jönköping University, SE‑553 18 Jönköping, Sweden, Department of Medical Cell Biology, Uppsala University, SE‑752 36 Uppsala, Sweden

Copyright: © Alehagen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Article Number: 127
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Published online on: December 7, 2020

https://doi.org/10.3892/etm.2020.9559
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Abstract

One of the major causes of mortality in the western hemisphere is cardiovascular disease. Therefore, a variety of markers to identify those at risk are required. Interleukin‑32 (IL‑32) is a cytokine that is associated with inflammation. The aim of the current study was to investigate variations in single nucleotide polymorphisms (SNPs) of IL‑32 and plasma expression, and their associations with mortality. A population of 486 elderly community‑living persons were evaluated. The participants were followed for 7.1 years and underwent a clinical examination and blood sampling. SNP analyses of IL‑32 rs28372698 using allelic discrimination and plasma measurement of IL‑32, using ELISA, were performed. During the follow‑up period, 140 (28.8%) all‑cause and 87 (17.9%) cardiovascular deaths were registered. No significant difference between mortality and plasma concentration of IL‑32 was observed. The A/A genotype group exhibited significantly higher all‑cause mortality (P=0.036), and an almost two‑fold increased risk in a multivariate Cox regression model for all‑cause and cardiovascular mortality. A highly significant difference in all‑cause and cardiovascular mortality between the A/A and the T/T groups was demonstrated (P=0.015 resp. P=0.014). In the present study, the cytokine IL‑32 was demonstrated to have prognostic information, with an increased risk of all‑cause and cardiovascular mortality for those with the A/A genotype rs28372698 of IL‑32. The A/A genotype could therefore be regarded as a possible biomarker for mortality risk that may be used to offer optimized cardiovascular patient handling in the future. However, the present study sample was small, and the results should be regarded as hypothesis‑generating.

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1	Hong JT, Son DJ, Lee CK, Yoon DY, Lee DH, Yoon DY, Lee DH and Park MH: Interleukin 32, inflammation and cancer. Pharmacol Ther. 174:127–137. 2017.PubMed/NCBI View Article : Google Scholar
2	Gui M, Zhang H, Zhong K, Li Y, Sun J and Wang L: Clinical significance of interleukin-32 expression in patients with rheumatoid arthritis. Asian Pac J Allergy Immunol. 31:73–78. 2013.PubMed/NCBI
3	Arcaroli JJ, Liu N, Yi N and Abraham E: Association between IL-32 genotypes and outcome in infection-associated acute lung injury. Crit Care. 15(R138)2011.PubMed/NCBI View Article : Google Scholar
4	El-Far M, Kouassi P, Sylla M, Zhang Y, Fouda A, Fabre T, Goulet JP, van Grevenynghe J, Lee T, Singer J, et al: Proinflammatory isoforms of IL-32 as novel and robust biomarkers for control failure in HIV-infected slow progressors. Sci Rep. 6(22902)2016.PubMed/NCBI View Article : Google Scholar
5	Bao F, Wen X, Liu A, Dai X, Zhao Q, Wang Y and Lu S: Elevated levels of serum IL-32 in patients with active pulmonary tuberculosis. Afr J Microbiol Res. 6:7292–7294. 2012.
6	Plantinga TS, Costantini I, Heinhuis B, Huijbers A, Semango G, Kusters B, Netea MG, Hermus AR, Smit JW, Dinarello CA, et al: A promoter polymorphism in human interleukin-32 modulates its expression and influences the risk and the outcome of epithelial cell-derived thyroid carcinoma. Carcinogenesis. 34:1529–1535. 2013.PubMed/NCBI View Article : Google Scholar
7	Gonzalez-Hormazabal P, Musleh M, Bustamante M, Stambuk J, Escandar S, Valladares H, Lanzarini E, Chiong H, Rojas J, Castro VG, et al: Role of cytokine gene polymorphisms in gastric cancer risk in Chile. Anticancer Res. 34:3523–3530. 2014.PubMed/NCBI
8	Yu X, Zhou B, Zhang Z, Gao Q, Wang Y, Song Y, Pu Y, Chen Y, Duan R, Zhang L and Xi M: Significant association between IL-32 gene polymorphisms and susceptibility to endometrial cancer in Chinese Han women. Tumour Biol. 36:5265–5272. 2015.PubMed/NCBI View Article : Google Scholar
9	Wang Y, Zhou B, Zhao Y, Yu X, Liu Y and Zhang L: Association of plasma IL-32 levels and gene polymorphisms with systemic lupus erythematosus in Chinese Han population. Dis Markers. 2016(2460206)2016.PubMed/NCBI View Article : Google Scholar
10	Wang Y, Yang Y, Zhu Y, Li L, Chen F and Zhang L: Polymorphisms and expression of IL-32: Impact on genetic susceptibility and clinical outcome of lung cancer. Biomarkers. 22:165–170. 2017.PubMed/NCBI View Article : Google Scholar
11	Damen MS, Agca R, Holewijn S, de Graaf J, Dos Santos JC, van Riel PL, Fransen J, Coenen MJ, Nurmohamed MT, Netea MG, et al: IL-32 promoter SNP rs4786370 predisposes to modified lipoprotein profiles in patients with rheumatoid arthritis. Sci Rep. 7(41629)2017.PubMed/NCBI View Article : Google Scholar
12	Seo EH, Kang J, Kim KH, Cho MC, Lee S, Kim HJ, Kim JH, Kim EJ, Park DK, Kim SH, et al: Detection of expressed IL-32 in human stomach cancer using ELISA and immunostaining. J Microbiol Biotechnol. 18:1606–1612. 2008.PubMed/NCBI
13	Xuan W, Huang W, Wang R, Chen C, Chen Y, Wang Y and Tan X: Elevated circulating IL-32 presents a poor prognostic outcome in patients with heart failure after myocardial infarction. Int J Cardiol. 243:367–373. 2017.PubMed/NCBI View Article : Google Scholar
14	Alehagen U, Ericsson A and Dahlström U: Are there any significant differences between females and males in the management of heart failure? Gender aspects of an elderly population with symptoms associated with heart failure. J Card Fail. 15:501–507. 2009.PubMed/NCBI View Article : Google Scholar
15	Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, et al: 2013 ACCF/AHA guideline for the management of heart failure: Executive summary: A report of the American college of cardiology foundation/american heart association task force on practice guidelines. Circulation. 128:1810–1852. 2013.PubMed/NCBI View Article : Google Scholar
16	Qi H, Shen J and Zhou W: Up-regulation of long non-coding RNA THRIL in coronary heart disease: Prediction for disease risk, correlation with inflammation, coronary artery stenosis, and major adverse cardiovascular events. J Clin Lab Anal. 34(e23196)2020.PubMed/NCBI View Article : Google Scholar
17	Ebadi N, Ghafouri-Fard S, Taheri M, Arsang-Jang S and Omrani MD: Expression analysis of inflammatory response-associated genes in coronary artery disease. Arch Physiol Biochem: Jan. 8:1–7. 2020.PubMed/NCBIdoi: 10.1080/13813455.2019.1708953.
18	Das AA, Chakravarty D, Bhunia D, Ghosh S, Mandal PC, Siddiqui KN and Bandyopadhyay A: Elevated level of circulatory sTLT1 induces inflammation through SYK/MEK/ERK signalling in coronary artery disease. Clin Sci (Lond). 133:2283–2299. 2019.PubMed/NCBI View Article : Google Scholar
19	Kura B, Szeiffova Bacova B, Kalocayova B, Sykora M and Slezak J: Oxidative stress-responsive MicroRNAs in heart injury. Int J Mol Sci. 21(358)2020.PubMed/NCBI View Article : Google Scholar
20	Tzoulaki I, Castagné R, Boulangé CL, Karaman I, Chekmeneva E, Evangelou E, Ebbels TMD, Kaluarachchi MR, Chadeau-Hyam M, Mosen D, et al: Serum metabolic signatures of coronary and carotid atherosclerosis and subsequent cardiovascular disease. Eur Heart J. 40:2883–2896. 2019.PubMed/NCBI View Article : Google Scholar
21	Matsuzawa Y and Lerman A: Endothelial dysfunction and coronary artery disease: Assessment, prognosis, and treatment. Coron Artery Dis. 25:713–724. 2014.PubMed/NCBI View Article : Google Scholar
22	Anderson RD, Petersen JW, Mehta PK, Wei J, Johnson BD, Handberg EM, Kar S, Samuels B, Azarbal B, Kothawade K, et al: Prevalence of coronary endothelial and microvascular dysfunction in women with symptoms of ischemia and no obstructive coronary artery disease is confirmed by a new cohort: The NHLBI-sponsored women's ischemia syndrome evaluation-coronary vascular dysfunction (WISE-CVD). J Interv Cardiol. 2019(7169275)2019.PubMed/NCBI View Article : Google Scholar
23	Damen MSMA, Popa CD, Netea MG, Dinarello CA and Joosten LAB: Interleukin-32 in chronic inflammatory conditions is associated with a higher risk of cardiovascular diseases. Atherosclerosis. 264:83–91. 2017.PubMed/NCBI View Article : Google Scholar
24	Nold-Petry CA, Rudloff I, Baumer Y, Ruvo M, Marasco D, Botti P, Farkas L, Cho SX, Zepp JA, Azam T, et al: IL-32 promotes angiogenesis. J Immunol. 192:589–602. 2014.PubMed/NCBI View Article : Google Scholar
25	Shamoun L, Kolodziej B, Andersson RE and Dimberg J: Protein expression and genetic variation of IL32 and association with colorectal cancer in Swedish patients. Anticancer Res. 38:321–328. 2018.PubMed/NCBI View Article : Google Scholar