Gene Variants, MRNA and NOD1/2 Protein Levels in Tunisian Childhood Asthma

Overview

Journal Lung

Specialty Pulmonary Medicine

Date 2019 Mar 16

PMID 30874883

Citations 2

Authors

Rafik Belhaj

Wajih Kaabachi

Ikbel Khalfallah

Basma Hamdi

Kamel Hamzaoui

Agnes Hamzaoui

Affiliations

Soon will be listed here.

Abstract

Introduction: Asthma is a common respiratory childhood disease that results from an interaction between genetic, environmental and immunologic factors. The implication of nucleotide-binding and oligomerization domain 1 and 2 (NOD1/CARD4, NOD2/CARD15) was highlighted in many inflammatory diseases.

Methods: In this case-control study, we analyzed the association of three NOD2 polymorphisms and one NOD1 variant, in 338 Tunisian asthmatic children and 425 healthy Controls, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. We also assessed NOD1 and NOD2 mRNA and protein levels by qRT-PCR and ELISA techniques.

Results: The homozygous AA genotype of rs2075820 was a risk factor for asthma (OR 2.39). The influence of the E266K variant in the presence of the heterozygous AG genotype was higher in male than female groups. The homozygous AA genotype was a risk factor associated with asthma, for patients aged between 6 and 18 years OR 2.39, IC95% (1.04-5.49) p < 0.01. The mRNA expression of NOD1, but not NOD2, was enhanced in asthma patients compared to Controls. We noted a significant difference between asthmatics and healthy controls in NOD1 protein expression (asthma patients : 31.18 ± 10.9 pg/ml, Controls: 20.10 ± 2.58 pg/ml; p < 0.001).

Conclusions: The NOD1 rs2075820 variant was associated with a higher childhood asthma risk and the NOD1 expression at mRNA and protein levels was significantly increased in asthma patients.

Citing Articles

NOD-like receptors in asthma.

Alvarez-Simon D, Ait Yahia S, de Nadai P, Audousset C, Chamaillard M, Gomperts Boneca I Front Immunol. 2022; 13:928886.

PMID: 36189256 PMC: 9515552. DOI: 10.3389/fimmu.2022.928886.

Nucleotide-Oligomerizing Domain-1 Activation Exaggerates Cigarette Smoke-Induced Chronic Obstructive Pulmonary-Like Disease in Mice.

Han G, Li M, Du J, Chen Y, Xu C Int J Chron Obstruct Pulmon Dis. 2021; 16:2605-2615.

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References

Ege M, Strachan D, Cookson W, Moffatt M, Gut I, Lathrop M . Gene-environment interaction for childhood asthma and exposure to farming in Central Europe. J Allergy Clin Immunol. 2011; 127(1):138-44, 144.e1-4. DOI: 10.1016/j.jaci.2010.09.041. View

Kvarnhammar A, Petterson T, Cardell L . NOD-like receptors and RIG-I-like receptors in human eosinophils: activation by NOD1 and NOD2 agonists. Immunology. 2011; 134(3):314-25. PMC: 3209571. DOI: 10.1111/j.1365-2567.2011.03492.x. View

Duan W, Mehta A, Magalhaes J, Ziegler S, Dong C, Philpott D . Innate signals from Nod2 block respiratory tolerance and program T(H)2-driven allergic inflammation. J Allergy Clin Immunol. 2010; 126(6):1284-93.e10. PMC: 3058679. DOI: 10.1016/j.jaci.2010.09.021. View

Shin J, Kim S, Park Y . Role of NOD1-mediated signals in a mouse model of allergic rhinitis. Otolaryngol Head Neck Surg. 2012; 147(6):1020-6. DOI: 10.1177/0194599812461999. View

Wong C, Leung T, Chu I, Dong J, Lam Y, Kei Lam C . Aberrant expression of regulatory cytokine IL-35 and pattern recognition receptor NOD2 in patients with allergic asthma. Inflammation. 2014; 38(1):348-60. DOI: 10.1007/s10753-014-0038-4. View

Girardin S, Sansonetti P, Philpott D . Intracellular vs extracellular recognition of pathogens--common concepts in mammals and flies. Trends Microbiol. 2002; 10(4):193-9. DOI: 10.1016/s0966-842x(02)02334-x. View

Tuncer S, Fiorillo M, Sorrentino R . The multifaceted nature of NLRP12. J Leukoc Biol. 2014; 96(6):991-1000. DOI: 10.1189/jlb.3RU0514-265RR. View

Bijanzadeh M, Mahesh P, Ramachandra N . An understanding of the genetic basis of asthma. Indian J Med Res. 2011; 134:149-61. PMC: 3181014. View

Reijmerink N, Bottema R, Kerkhof M, Gerritsen J, Stelma F, Thijs C . TLR-related pathway analysis: novel gene-gene interactions in the development of asthma and atopy. Allergy. 2009; 65(2):199-207. DOI: 10.1111/j.1398-9995.2009.02111.x. View

10.

Onoyama S, Ihara K, Yamaguchi Y, Ikeda K, Yamaguchi K, Yamamura K . Genetic susceptibility to Kawasaki disease: analysis of pattern recognition receptor genes. Hum Immunol. 2012; 73(6):654-60. DOI: 10.1016/j.humimm.2012.03.011. View

11.

Laitinen T, Daly M, Rioux J, Kauppi P, Laprise C, Petays T . A susceptibility locus for asthma-related traits on chromosome 7 revealed by genome-wide scan in a founder population. Nat Genet. 2001; 28(1):87-91. DOI: 10.1038/ng0501-87. View

12.

Ogura Y, Inohara N, Benito A, Chen F, Yamaoka S, Nunez G . Nod2, a Nod1/Apaf-1 family member that is restricted to monocytes and activates NF-kappaB. J Biol Chem. 2000; 276(7):4812-8. DOI: 10.1074/jbc.M008072200. View

13.

McGovern D, Hysi P, Ahmad T, van Heel D, Moffatt M, Carey A . Association between a complex insertion/deletion polymorphism in NOD1 (CARD4) and susceptibility to inflammatory bowel disease. Hum Mol Genet. 2005; 14(10):1245-50. DOI: 10.1093/hmg/ddi135. View

14.

Weidinger S, Klopp N, Rummler L, Wagenpfeil S, Novak N, Baurecht H . Association of NOD1 polymorphisms with atopic eczema and related phenotypes. J Allergy Clin Immunol. 2005; 116(1):177-84. DOI: 10.1016/j.jaci.2005.02.034. View

15.

Brickey W, Alexis N, Hernandez M, Reed W, Ting J, Peden D . Sputum inflammatory cells from patients with allergic rhinitis and asthma have decreased inflammasome gene expression. J Allergy Clin Immunol. 2011; 128(4):900-3. PMC: 3185200. DOI: 10.1016/j.jaci.2011.08.012. View

16.

Kharwar N, Prasad K, Paliwal V, Modi D . Association of NOD1 and NOD2 polymorphisms with Guillain-Barré syndrome in Northern Indian population. J Neurol Sci. 2016; 363:57-62. DOI: 10.1016/j.jns.2016.02.028. View

17.

Ait Yahia S, Azzaoui I, Everaere L, Vorng H, Chenivesse C, Marquillies P . CCL17 production by dendritic cells is required for NOD1-mediated exacerbation of allergic asthma. Am J Respir Crit Care Med. 2014; 189(8):899-908. DOI: 10.1164/rccm.201310-1827OC. View

18.

Feki S, Bouzid D, Abida O, Chtourou L, Elloumi N, Toumi A . Genetic association and phenotypic correlation of TLR4 but not NOD2 variants with Tunisian inflammatory bowel disease. J Dig Dis. 2017; 18(11):625-633. DOI: 10.1111/1751-2980.12552. View

19.

Ogura Y, Bonen D, Inohara N, Nicolae D, Chen F, Ramos R . A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature. 2001; 411(6837):603-6. DOI: 10.1038/35079114. View

20.

Molnar T, Hofner P, Nagy F, Lakatos P, Fischer S, LAKATOS L . NOD1 gene E266K polymorphism is associated with disease susceptibility but not with disease phenotype or NOD2/CARD15 in Hungarian patients with Crohn's disease. Dig Liver Dis. 2007; 39(12):1064-70. DOI: 10.1016/j.dld.2007.09.003. View