Analysis of IL-12 P40 Subunit Gene and IFN-gamma G5644A Polymorphisms in Idiopathic Pulmonary Fibrosis

Overview

Journal Respir Res

Specialty Pulmonary Medicine

Date 2003 Aug 14

PMID 12914676

Citations 13

Authors

Panagiota Latsi

Panagiotis Pantelidis

Dimitris Vassilakis

Hiroe Sato

Kenneth I Welsh

Roland M du Bois

Affiliations

Soon will be listed here.

Abstract

Background: Genes encoding cytokine mediators are prime candidates for genetic analysis in conditions with T-helper (Th) cell disease driven imbalance. Idiopathic Pulmonary Fibrosis (IPF) is a predominantly Th2 mediated disease associated with a paucity of interferon-gamma (IFN-gamma). The paucity of IFN-gamma may favor the development of progressive fibrosis in IPF. Interleukin-12 (IL-12) plays a key role in inducing IFN-gamma production. The aim of the current study was to assess whether the 1188 (A/C) 3'UTR single nucleotide polymorphism (SNP) in the IL-12 p40 subunit gene which was recently found to be functional and the 5644 (G/A) 3' UTR SNP of the IFN-gamma gene were associated with susceptibility to IPF.

Methods: We investigated the allelic distribution in these loci in UK white Caucasoid subjects comprising 73 patients with IPF and 157 healthy controls. The SNPs were determined using the polymerase chain reaction in association with sequence-specific primers incorporating mismatches at the 3'-end.

Results: Our results showed that these polymorphisms were distributed similarly in the IPF and control groups

Conclusion: We conclude that these two potentially important candidate gene single nucleotide polymorphisms are not associated with susceptibility to IPF.

Citing Articles

Identification and Analysis of Key Immune- and Inflammation-Related Genes in Idiopathic Pulmonary Fibrosis.

Tan Y, Qian B, Ma Q, Xiang K, Wang S J Inflamm Res. 2025; 18:1993-2009.

PMID: 39959639 PMC: 11829586. DOI: 10.2147/JIR.S489210.

Psoriasis may increase the risk of idiopathic pulmonary fibrosis: a two-sample Mendelian randomization study.

Chen L, Wei Y, Hu M, Liu Y, Zheng X Respir Res. 2024; 25(1):101.

PMID: 38403646 PMC: 10895777. DOI: 10.1186/s12931-024-02721-5.

The mitochondrial cardiolipin remodeling enzyme lysocardiolipin acyltransferase is a novel target in pulmonary fibrosis.

Huang L, Mathew B, Li H, Zhao Y, Ma S, Noth I Am J Respir Crit Care Med. 2014; 189(11):1402-15.

PMID: 24779708 PMC: 4098083. DOI: 10.1164/rccm.201310-1917OC.

ADAM33 gene polymorphisms are associated with the risk of idiopathic pulmonary fibrosis.

Uh S, Jang A, Park S, Park J, Min C, Kim Y Lung. 2014; 192(4):525-32.

PMID: 24728305 DOI: 10.1007/s00408-014-9578-5.

Cytokine gene polymorphisms and serum cytokine levels in patients with idiopathic pulmonary fibrosis.

Alhamad E, Cal J, Shakoor Z, Almogren A, AlBoukai A BMC Med Genet. 2013; 14:66.

PMID: 23815594 PMC: 3700855. DOI: 10.1186/1471-2350-14-66.

References

Cher D, Mosmann T . Two types of murine helper T cell clone. II. Delayed-type hypersensitivity is mediated by TH1 clones. J Immunol. 1987; 138(11):3688-94. View

Czaja M, Weiner F, Giambrone M, Eghbali M, Zern M . Differential effects of gamma-interferon on collagen and fibronectin gene expression. J Biol Chem. 1987; 262(27):13348-51. View

Mosmann T, Cherwinski H, Bond M, Giedlin M, Coffman R . Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986; 136(7):2348-57. View

Bream J, Carrington M, OToole S, Dean M, Gerrard B, Shin H . Polymorphisms of the human IFNG gene noncoding regions. Immunogenetics. 2000; 51(1):50-8. DOI: 10.1007/s002510050008. View

Pantelidis P, Jones M, Welsh K, Taylor A, du Bois R . Identification of four novel interleukin-13 gene polymorphisms. Genes Immun. 2001; 1(5):341-5. DOI: 10.1038/sj.gene.6363679. View

Hall M, McGlinn E, Coakley G, Fisher S, Boki K, Middleton D . Genetic polymorphism of IL-12 p40 gene in immune-mediated disease. Genes Immun. 2001; 1(3):219-24. DOI: 10.1038/sj.gene.6363661. View

Huang D, Cancilla M, Morahan G . Complete primary structure, chromosomal localisation, and definition of polymorphisms of the gene encoding the human interleukin-12 p40 subunit. Genes Immun. 2001; 1(8):515-20. DOI: 10.1038/sj.gene.6363720. View

Morahan G, Huang D, Ymer S, Cancilla M, Stephen K, Dabadghao P . Linkage disequilibrium of a type 1 diabetes susceptibility locus with a regulatory IL12B allele. Nat Genet. 2001; 27(2):218-21. DOI: 10.1038/84872. View

Pantelidis P, Fanning G, Wells A, Welsh K, du Bois R . Analysis of tumor necrosis factor-alpha, lymphotoxin-alpha, tumor necrosis factor receptor II, and interleukin-6 polymorphisms in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2001; 163(6):1432-6. DOI: 10.1164/ajrccm.163.6.2006064. View

10.

van Veen T, Crusius J, Schrijver H, Bouma G, Killestein J, van Winsen L . Interleukin-12p40 genotype plays a role in the susceptibility to multiple sclerosis. Ann Neurol. 2001; 50(2):275. DOI: 10.1002/ana.1107. View

11.

Seegers D, Zwiers A, Strober W, Pena A, Bouma G . A TaqI polymorphism in the 3'UTR of the IL-12 p40 gene correlates with increased IL-12 secretion. Genes Immun. 2002; 3(7):419-23. DOI: 10.1038/sj.gene.6363919. View

12.

Uboldi de Capei M, Dametto E, Fasano M, Rendine S, Curtoni E . Genotyping for cytokine polymorphisms: allele frequencies in the Italian population. Eur J Immunogenet. 2003; 30(1):5-10. DOI: 10.1046/j.1365-2370.2003.00361.x. View

13.

Rosenbloom J, Feldman G, Freundlich B, Jimenez S . Transcriptional control of human diploid fibroblast collagen synthesis by gamma-interferon. Biochem Biophys Res Commun. 1984; 123(1):365-72. DOI: 10.1016/0006-291x(84)90422-4. View

14.

Kuroki S, Ohta A, Sueoka N, Katoh O, Yamada H, Yamaguchi M . Determination of various cytokines and type III procollagen aminopeptide levels in bronchoalveolar lavage fluid of the patients with pulmonary fibrosis: inverse correlation between type III procollagen aminopeptide and interferon-gamma in.... Br J Rheumatol. 1995; 34(1):31-6. DOI: 10.1093/rheumatology/34.1.31. View

15.

Bitterman P, Rennard S, Keogh B, Wewers M, Adelberg S, Crystal R . Familial idiopathic pulmonary fibrosis. Evidence of lung inflammation in unaffected family members. N Engl J Med. 1986; 314(21):1343-7. DOI: 10.1056/NEJM198605223142103. View

16.

Hyde D, Henderson T, Giri S, Tyler N, Stovall M . Effect of murine gamma interferon on the cellular responses to bleomycin in mice. Exp Lung Res. 1988; 14(5):687-704. DOI: 10.3109/01902148809087837. View

17.

Prior C, Haslam P . In vivo levels and in vitro production of interferon-gamma in fibrosing interstitial lung diseases. Clin Exp Immunol. 1992; 88(2):280-7. PMC: 1554282. DOI: 10.1111/j.1365-2249.1992.tb03074.x. View

18.

Romagnani S . Induction of TH1 and TH2 responses: a key role for the 'natural' immune response?. Immunol Today. 1992; 13(10):379-81. DOI: 10.1016/0167-5699(92)90083-J. View

19.

Majumdar S, Li D, Ansari T, Pantelidis P, Black C, Gizycki M . Different cytokine profiles in cryptogenic fibrosing alveolitis and fibrosing alveolitis associated with systemic sclerosis: a quantitative study of open lung biopsies. Eur Respir J. 1999; 14(2):251-7. DOI: 10.1034/j.1399-3003.1999.14b03.x. View

20.

Tanaka Y, Nakashima H, Hisano C, Kohsaka T, Nemoto Y, Niiro H . Association of the interferon-gamma receptor variant (Val14Met) with systemic lupus erythematosus. Immunogenetics. 1999; 49(4):266-71. DOI: 10.1007/s002510050492. View