Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Infectious Diseases
Published in: BMC Infectious Diseases 1/2021

Open Access 01-12-2021 | Research

Association between risk of brucellosis and genetic variations in MicroRNA-146a

Authors: Sima Kazemi, Saeid Afshar, Manoochehr Karami, Massoud Saidijam, Fariba Keramat, Seyed Hamid Hashemi, Mohammad Yousef Alikhani

Published in: BMC Infectious Diseases | Issue 1/2021

Login to get access

Abstract

Background

Single nucleotide polymorphisms (SNPs) are the most common types of DNA changes in the human genome that leading to phenotypic differences in humans. MicroRNAs (miRNAs) are usually affected by various bacterial infections, and they are involved in controlling the immune responses. MicroRNA-146a (miR-146a) plays an essential role in the development of infectious and inflammatory diseases. The aim of the present study was to investigate the association between risk of brucellosis and genetic variations in miR-146a.

Methods

This case–control study was conducted on 108 Brucellosis patients and 108 healthy controls. We genotyped two SNPs (rs2910164 and rs57095329) of the miR-146a using tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) and restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) methods.

Results

The rs2910164 SNP was significantly associated with brucellosis in co-dominant [OR = 4.27, 95% CI = (2.35–7.79, P = 0.001] and dominant [OR = 3.52, 95% CI = (1.97–6.30, P = 0.001] models. Co-dominant (P = 0.047) and recessive (P = 0.018) models were significant at position rs57095329 between the two groups of patient and healthy. The A C haplotype (rs2910164 and rs57095329) was associated with brucellosis in the assessed population [OR (95% CI) = 1.98 (1.22–3.20), P = 0.0059].

Conclusions

Consequently, our study demonstrated significant differences in genotype and haplotype frequencies of miR-146a variants between brucellosis patients and controls. Further studies on the larger sample sizes are required to verify the observed associations.
Literature
1.
Xavier M, Paixão T, Poester F, Lage A, Santos R. Pathological, immunohistochemical and bacteriological study of tissues and milk of cows and fetuses experimentally infected with Brucella abortus. J Comp Pathol. 2009;140(2–3):149–57.PubMedCrossRef
2.
Pappas G, Panagopoulou P, Christou L, Akritidis N. Biological weapons. Cell Mol Life Sci CMLS. 2006;63(19–20):2229–36.PubMedCrossRef
3.
Atluri VL, Xavier MN, De Jong MF, Den Hartigh AB, Tsolis RM. Interactions of the human pathogenic Brucella species with their hosts. Annu Rev Microbiol. 2011;65:523–41.PubMedCrossRef
4.
Xavier MN, Paixao TA, den Hartigh AB, Tsolis RM, Santos RL. Pathogenesis of Brucella spp. Open Veterinary Sci J 2010; 4(1).
5.
Hashemi SH, Keramat F, Ranjbar M, Mamani M, Farzam A, Jamal-Omidi S. Osteoarticular complications of brucellosis in Hamedan, an endemic area in the west of Iran. Int J Infect Dis. 2007;11(6):496–500.PubMedCrossRef
6.
Asiimwe BB, Kansiime C, Rwego IB. Risk factors for human brucellosis in agro-pastoralist communities of south western Uganda: a case–control study. BMC Res Notes. 2015;8(1):405.PubMedPubMedCentralCrossRef
7.
Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75(5):843–54.PubMedCrossRef
8.
Kong YW, Ferland-McCollough D, Jackson TJ, Bushell M. microRNAs in cancer management. Lancet Oncol. 2012;13(6):e249–58.PubMedCrossRef
9.
10.
Li Z, Rana TM. Therapeutic targeting of microRNAs: current status and future challenges. Nat Rev Drug Discovery. 2014;13(8):622–38.PubMedCrossRef
11.
Kunej T, Godnic I, Horvat S, Zorc M, Calin GA. Cross talk between microRNA and coding cancer genes. Cancer J (Sudbury, Mass). 2012;18(3):223.CrossRef
12.
13.
Staedel C, Darfeuille F. Micro RNA s and bacterial infection. Cell Microbiol. 2013;15(9):1496–507.PubMedCrossRef
14.
Eulalio A, Schulte L, Vogel J. The mammalian microRNA response to bacterial infections. RNA Biol. 2012;9(6):742–50.PubMedCrossRef
15.
16.
Zhou X, Li X, Ye Y, Zhao K, Zhuang Y, Li Y, Wei Y, Wu M. MicroRNA-302b augments host defense to bacteria by regulating inflammatory responses via feedback to TLR/IRAK4 circuits. Nat Commun. 2014;5(1):1–14.
17.
Sunkavalli U, Aguilar C, Silva RJ, Sharan M, Cruz AR, Tawk C, Maudet C, Mano M, Eulalio A. Analysis of host microRNA function uncovers a role for miR-29b-2–5p in Shigella capture by filopodia. PLoS Pathog. 2017;13(4):e1006327.PubMedPubMedCentralCrossRef
18.
Rothchild AC, Sissons JR, Shafiani S, Plaisier C, Min D, Mai D, Gilchrist M, Peschon J, Larson RP, Bergthaler A. MiR-155–regulated molecular network orchestrates cell fate in the innate and adaptive immune response to Mycobacterium tuberculosis. Proc Natl Acad Sci. 2016;113(41):E6172–81.PubMedPubMedCentralCrossRef
19.
Oertli M, Engler DB, Kohler E, Koch M, Meyer TF, Müller A. MicroRNA-155 is essential for the T cell-mediated control of Helicobacter pylori infection and for the induction of chronic Gastritis and Colitis. J Immunol. 2011;187(7):3578–86.PubMedCrossRef
20.
Mirzaei R, Mohammadzadeh R, Mirzaei H, Sholeh M, Karampoor S, Abdi M, Alikhani MY, Kazemi S, Ahmadyousefi Y, Jalalifar S. Role of microRNAs in Staphylococcus aureus infection: potential biomarkers and mechanism. IUBMB Life 2020.
21.
Lou J, Wang Y, Zhang Z, Qiu W. MiR-20b inhibits mycobacterium tuberculosis induced inflammation in the lung of mice through targeting NLRP3. Exp Cell Res. 2017;358(2):120–8.PubMedCrossRef
22.
Kumar M, Sahu SK, Kumar R, Subuddhi A, Maji RK, Jana K, Gupta P, Raffetseder J, Lerm M, Ghosh Z. MicroRNA let-7 modulates the immune response to Mycobacterium tuberculosis infection via control of A20, an inhibitor of the NF-κB pathway. Cell Host Microbe. 2015;17(3):345–56.PubMedCrossRef
23.
Jingjing Z, Nan Z, Wei W, Qinghe G, Weijuan W, Peng W, Xiangpeng W. MicroRNA-24 modulates Staphylococcus aureus-induced macrophage polarization by suppressing CHI3L1. Inflammation. 2017;40(3):995–1005.PubMedCrossRef
24.
Izar B, Mannala GK, Mraheil MA, Chakraborty T, Hain T. microRNA response to Listeria monocytogenes infection in epithelial cells. Int J Mol Sci. 2012;13(1):1173–85.PubMedPubMedCentralCrossRef
25.
Aguilar C, Mano M, Eulalio A. MicroRNAs at the host–bacteria interface: host defense or bacterial offense. Trends Microbiol. 2019;27(3):206–18.PubMedCrossRef
26.
27.
Butler JM. Single nucleotide polymorphisms and applications. Advanced Topics in Forensic DNA Typing, Academic Press, California, USA 2012:347–369.
28.
Bosetti C, Levi F, Rosato V, Bertuccio P, Lucchini F, Negri E, La Vecchia C. Recent trends in colorectal cancer mortality in Europe. Int J Cancer. 2011;129(1):180–91.PubMedCrossRef
29.
O’connell RM, Rao DS, Chaudhuri AA, Baltimore D. Physiological and pathological roles for microRNAs in the immune system. Nat Rev Immunol. 2010;10(2):111–22.PubMedCrossRef
30.
Zilahi E, Tarr T, Papp G, Griger Z, Sipka S, Zeher M. Increased microRNA-146a/b, TRAF6 gene and decreased IRAK1 gene expressions in the peripheral mononuclear cells of patients with Sjögren’s syndrome. Immunol Lett. 2012;141(2):165–8.PubMedCrossRef
31.
Spinelli SV, Diaz A, D’Attilio L, Marchesini MM, Bogue C, Bay ML, Bottasso OA. Altered microRNA expression levels in mononuclear cells of patients with pulmonary and pleural tuberculosis and their relation with components of the immune response. Mol Immunol. 2013;53(3):265–9.PubMedCrossRef
32.
33.
Liu Y, Wang X, Jiang J, Cao Z, Yang B, Cheng X. Modulation of T cell cytokine production by miR-144* with elevated expression in patients with pulmonary tuberculosis. Mol Immunol. 2011;48(9–10):1084–90.PubMedCrossRef
34.
Zhou Q, Hou S, Liang L, Li X, Tan X, Wei L, Lei B, Kijlstra A, Yang P. MicroRNA-146a and Ets-1 gene polymorphisms in ocular Behçet’s disease and Vogt–Koyanagi–Harada syndrome. Ann Rheum Dis. 2014;73(1):170–6.PubMedCrossRef
35.
Shao Y, Li J, Cai Y, Xie Y, Ma G, Li Y, Chen Y, Liu G, Zhao B, Cui L. The functional polymorphisms of miR-146a are associated with susceptibility to severe sepsis in the Chinese population. Mediators Inflammation 2014; 2014.
36.
Luo X, Yang W, Ye D-Q, Cui H, Zhang Y, Hirankarn N, Qian X, Tang Y, Lau YL, De Vries N. A functional variant in microRNA-146a promoter modulates its expression and confers disease risk for systemic lupus erythematosus. PLoS Genet. 2011;7(6):e1002128.PubMedPubMedCentralCrossRef
37.
Li Y, Du C, Wang W, Ma G, Cui L, Zhou H, Tao H, Yao L, Zhao B, Li K. Genetic association of MiR-146a with multiple sclerosis susceptibility in the Chinese population. Cell Physiol Biochem. 2015;35(1):281–91.PubMedCrossRef
38.
39.
Labib DA, Shaker OG, El Refai RM, Ghoniem SA, Elmazny A. Association between miRNA-146a and polymorphisms of its target gene, IRAK1, regarding susceptibility to and clinical features of systemic lupus erythematous and multiple sclerosis. Lab Med. 2019;50(1):34–41.PubMedCrossRef
40.
Hung P-S, Chang K-W, Kao S-Y, Chu T-H, Liu C-J, Lin S-C. Association between the rs2910164 polymorphism in pre-mir-146a and oral carcinoma progression. Oral Oncol. 2012;48(5):404–8.PubMedCrossRef
41.
Cui L, Li Y, Ma G, Wang Y, Cai Y, Liu S, Chen Y, Li J, Xie Y, Liu G. A functional polymorphism in the promoter region of microRNA-146a is associated with the risk of Alzheimer disease and the rate of cognitive decline in patients. PLoS ONE. 2014;9(2):e89019.PubMedPubMedCentralCrossRef
42.
Iwai N, Naraba H. Polymorphisms in human pre-miRNAs. Biochem Biophys Res Commun. 2005;331(4):1439–44.PubMedCrossRef
43.
Xu T, Zhu Y, Wei Q-K, Yuan Y, Zhou F, Ge Y-Y, Yang J-R, Su H, Zhuang S-M. A functional polymorphism in the miR-146a gene is associated with the risk for hepatocellular carcinoma. Carcinogenesis. 2008;29(11):2126–31.PubMedCrossRef
44.
Duval M, Cossart P, Lebreton A. Mammalian microRNAs and long noncoding RNAs in the host-bacterial pathogen crosstalk. In: Seminars in cell & developmental biology: 2017: Elsevier; 2017: 11–19.
45.
Kazemi S, Saidijam M, Hashemi SH, Karami M, Vaisi-Raygani A, Alikhani MY. Analysis of IL-10 and IL-6 gene polymorphisms and their serum levels in patients with brucellosis: a case control study. Immunol Invest. 2016;45(2):107–15.PubMedCrossRef
46.
Majzoobi MM, Hashemi SH, Mamani M, Keramat F, Poorolajal J, Basir HRG. Effect of hydroxychloroquine on treatment and recurrence of acute brucellosis: a single-blind, randomized clinical trial. Int J Antimicrob Agents. 2018;51(3):365–9.PubMedCrossRef
47.
48.
Hashemi M, Moradi N, Ziaee SAM, Narouie B, Soltani MH, Rezaei M, Shahkar G, Taheri M. Association between single nucleotide polymorphism in miR-499, miR-196a2, miR-146a and miR-149 and prostate cancer risk in a sample of Iranian population. J Adv Res. 2016;7(3):491–8.PubMedPubMedCentralCrossRef
49.
Wei L, Zhou Q, Hou S, Bai L, Liu Y, Qi J, Xiang Q, Zhou Y, Kijlstra A, Yang P. MicroRNA-146a and Ets-1 gene polymorphisms are associated with pediatric uveitis. PLoS ONE. 2014;9(3):e91199.PubMedPubMedCentralCrossRef
50.
51.
Taganov KD, Boldin MP, Chang K-J, Baltimore D. NF-κB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci. 2006;103(33):12481–6.PubMedPubMedCentralCrossRef
52.
53.
Maudet C, Mano M, Eulalio A. MicroRNAs in the interaction between host and bacterial pathogens. FEBS Lett. 2014;588(22):4140–7.PubMedCrossRef
54.
55.
O’neill LA, Sheedy FJ, McCoy CE. MicroRNAs: the fine-tuners of Toll-like receptor signalling. Nat Rev Immunol. 2011;11(3):163–75.PubMedCrossRef
56.
Soleimani A, Ghanadi K, Noormohammadi Z, Irani S. The correlation between miR-146a C/G polymorphism and UHRF1 gene expression level in gastric tumor. J Dig Dis. 2016;17(3):169–74.PubMedCrossRef
57.
Ramkaran P, Khan S, Phulukdaree A, Moodley D, Chuturgoon AA. miR-146a polymorphism influences levels of miR-146a, IRAK-1, and TRAF-6 in young patients with coronary artery disease. Cell Biochem Biophys. 2014;68(2):259–66.PubMedCrossRef
58.
Kupcinskas J, Wex T, Link A, Leja M, Bruzaite I, Steponaitiene R, Juzenas S, Gyvyte U, Ivanauskas A, Ancans G. Gene polymorphisms of micrornas in Helicobacter pylori-induced high risk atrophic gastritis and gastric cancer. PLoS ONE. 2014;9(1):e87467.PubMedPubMedCentralCrossRef
59.
Hezova R, Kovarikova A, Bienertova-Vasku J, Sachlova M, Redova M, Vasku A, Svoboda M, Radova L, Kiss I, Vyzula R. Evaluation of SNPs in miR-196-a2, miR-27a and miR-146a as risk factors of colorectal cancer. World J Gastroenterol: WJG. 2012;18(22):2827.PubMedPubMedCentralCrossRef
60.
Cezar-de-Mello PF, Toledo-Pinto TG, Marques CS, Arnez LE, Cardoso CC, Guerreiro LT, Antunes SL, Jardim MM, de Covas CJM, Illaramendi X. Pre-miR-146a (rs2910164 G> C) single nucleotide polymorphism is genetically and functionally associated with leprosy. PLoS Negl Trop Dis. 2014;8(9):e3099.PubMedPubMedCentralCrossRef
61.
Bogunia-Kubik K, Wysoczańska B, Piątek D, Iwaszko M, Ciechomska M, Świerkot J. Significance of polymorphism and expression of miR-146a and NFkB1 genetic variants in patients with rheumatoid arthritis. Arch Immunol Ther Exp. 2016;64(1):131–6.CrossRef
62.
Xion Y, Chen S, Chen R, Lin W, Ni J. Association between microRNA polymorphisms and humoral immunity to hepatitis B vaccine. Hum Vaccin Immunother. 2013;9(8):1673–8.PubMedCentralCrossRef
63.
Song M-y, Su H-j, Zhang L, Ma J-l, Li J-y, Pan K-f, You W-c. Genetic polymorphisms of miR-146a and miR-27a, H. pylori infection, and risk of gastric lesions in a Chinese population. PLoS ONE. 2013;8(4):e61250.PubMedPubMedCentralCrossRef
64.
Shankaran ZS, Walter CEJ, Ramanathan A, Dandapani MC, Selvaraj S, Kontham SS, Johnson T. microRNA-146a gene polymorphism alters human colorectal cancer susceptibility and influences the expression of its target genes in toll-like receptor (TLR) pathway. Meta Gene. 2020;24:100654.CrossRef
65.
Zhang X, Li Y, Li X, Zhang W, Pan Z, Wu F, Wang C, Chen Z, Jiang T, Xu D. Association of the miR-146a, miR-149, miR-196a2 and miR-499 polymorphisms with susceptibility to pulmonary tuberculosis in the Chinese Uygur, Kazak and Southern Han populations. BMC Infect Dis. 2015;15(1):41.PubMedPubMedCentralCrossRef
66.
Damodaran M, Paul SF, Venkatesan V. Genetic polymorphisms in miR-146a, miR-196a2 and miR-125a genes and its association in prostate cancer. Pathol Oncol Res. 2020;26(1):193–200.PubMedCrossRef
67.
Cui L, Tao H, Wang Y, Liu Z, Xu Z, Zhou H, Cai Y, Yao L, Chen B, Liang W. A functional polymorphism of the microRNA-146a gene is associated with susceptibility to drug-resistant epilepsy and seizures frequency. Seizure. 2015;27:60–5.PubMedCrossRef
Metadata
Title
Association between risk of brucellosis and genetic variations in MicroRNA-146a
Authors
Sima Kazemi
Saeid Afshar
Manoochehr Karami
Massoud Saidijam
Fariba Keramat
Seyed Hamid Hashemi
Mohammad Yousef Alikhani
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2021
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-021-06775-4

Other articles of this Issue 1/2021

BMC Infectious Diseases 1/2021 Go to the issue

Research

Ultraviolet C lamps for disinfection of surfaces potentially contaminated with SARS-CoV-2 in critical hospital settings: examples of their use and some practical advice

Case report

Tenosynovitis caused by Mycobacterium marseillense, initially identified as Mycobacterium avium complex using AccuProbe and COBAS TaqMan

Technical advance

An emm-type specific qPCR to track bacterial load during experimental human Streptococcus pyogenes pharyngitis

Research article

Impact of delays to incubation and storage temperature on blood culture results: a multi-centre study

Correction

Correction to: Impact of 16S rDNA sequencing on clinical treatment decisions: a single center retrospective study

Technical advance

Combining stool and stories: exploring antimicrobial resistance among a longitudinal cohort of international health students
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits