Advertisement

Genes & Genomics

, Volume 41, Issue 4, pp 389–395 | Cite as

Association between CD53 genetic polymorphisms and tuberculosis cases

  • Hyun-Seok Jin
  • Jang-Eun Cho
  • Sangjung ParkEmail author
Research Article

Abstract

Background

Tetraspanin proteins are expressed in various immune cells, and they play an important role in tuberculosis formation. CD53 is a protein in the tetraspanin family that is expressed in many white blood cells. In particular, it plays an important role in cytokine regulation and interaction between natural killer (NK) cells and antigen-presenting cells (APCs).

Objectives

The purpose of this study was to investigate whether the single nucleotide polymorphisms (SNPs) difference of CD53 gene could affect TB case.

Methods

In this study, we investigated the effects of genetic polymorphism of CD53 on the pathogenesis of tuberculosis based on Korean Association Resource (KARE) data. Logistic regression analysis was used to determine the effect of SNPs of the CD53 gene on tuberculosis in TB cases and control groups. We also examined the effect of SNPs on tuberculosis in gene expression.

Results

Eight SNPs of CD53 were found to be associated with TB case. The SNP showing the greatest significance in this association was rs4839583 (odds ratio = 0.83, 95% confidence interval 0.72–0.96, p = 0.010). These genetic variants might be involved in cytokine regulation through the Jun pathway, and are thought to affect the immune responses and pathogenesis of TB.

Discussion

CD53 is a type of tetraspanin that is expressed on various immune cells. In this study, we identified eight statistically significant SNPs in CD53 gene, confirming that it could be involved in the regulation of CD53 gene expression.

Conclusion

Associations between genetic variants and tuberculosis facilitated better understanding of the differences in the incidence of tuberculosis in various populations.

Keywords

Tuberculosis Mycobacterium tuberculosis CD53 Tetraspanin SNP 

Notes

Acknowledgements

This research was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT and Future Planning (2017R1C1B5016589).

Compliance with ethical standards

Conflict of interest

Hyun-Seok Jin, Jang-Eun Cho and Sangjung Park declare that they have no conflict of interest.

Ethical approval

This study had been approved by the institutional review board of the Korean National Institute of Health (KNIH) and Hoseo University (1041231-170221-HR-055-01). Informed consent was obtained from all individual participants included in the study.

References

  1. Bos SD, Lakenberg N, van der Breggen R, Houwing-Duistermaat JJ, Kloppenburg M, de Craen AJ, Beekman M, Meulenbelt I, Slagboom PE (2010) A genome-wide linkage scan reveals CD53 as an important regulator of innate TNF-alpha levels. Eur J Hum Genet 18:953–959CrossRefGoogle Scholar
  2. Bosca L, Lazo PA (1994) Induction of nitric oxide release by MRC OX-44 (anti-CD53) through a protein kinase C-dependent pathway in rat macrophages. J Exp Med 179:1119–1126CrossRefGoogle Scholar
  3. Chimusa ER, Zaitlen N, Daya M, Moller M, van Helden PD, Mulder NJ, Price AL, Hoal EG (2014) Genome-wide association study of ancestry-specific TB risk in the South African coloured population. Hum Mol Genet 23:796–809CrossRefGoogle Scholar
  4. Cho YS, Go MJ, Kim YJ, Heo JY, Oh JH, Ban HJ, Yoon D, Lee MH, Kim DJ, Park M et al (2009) A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits. Nat Genet 41:527–534CrossRefGoogle Scholar
  5. Davis RJ (2000) Signal transduction by the JNK group of MAP kinases. Cell 103:239–252CrossRefGoogle Scholar
  6. International HapMap Consortium (2003) The International HapMap Project. Nature 426:789–796CrossRefGoogle Scholar
  7. Lee HM, Shin DM, Kim KK, Lee JS, Paik TH, Jo EK (2009) Roles of reactive oxygen species in CXCL8 and CCL2 expression in response to the 30-kDa antigen of Mycobacterium tuberculosis. J Clin Immunol 29:46–56CrossRefGoogle Scholar
  8. Lee H, Bae S, Jang J, Choi BW, Park CS, Park JS, Lee SH, Yoon Y (2013) CD53, a suppressor of inflammatory cytokine production, is associated with population asthma risk via the functional promoter polymorphism -1560 C> T. Biochim Biophys Acta 1830:3011–3018CrossRefGoogle Scholar
  9. Li Y, Willer CJ, Ding J, Scheet P, Abecasis GR (2010) MaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypes. Genet Epidemiol 34:816–834CrossRefGoogle Scholar
  10. Maecker HT, Todd SC, Levy S (1997) The tetraspanin superfamily: molecular facilitators. FASEB J 11:428–442CrossRefGoogle Scholar
  11. Mahasirimongkol S, Yanai H, Mushiroda T, Promphittayarat W, Wattanapokayakit S, Phromjai J, Yuliwulandari R, Wichukchinda N, Yowang A, Yamada N et al (2012) Genome-wide association studies of tuberculosis in Asians identify distinct at-risk locus for young tuberculosis. J Hum Genet 57:363–367CrossRefGoogle Scholar
  12. Moller M, Hoal EG (2010) Current findings, challenges and novel approaches in human genetic susceptibility to tuberculosis. Tuberculosis (Edinb) 90:71–83CrossRefGoogle Scholar
  13. Mollinedo F, Fontan G, Barasoain I, Lazo PA (1997) Recurrent infectious diseases in human CD53 deficiency. Clin Diagn Lab Immunol 4:229–231Google Scholar
  14. Mootoo A, Stylianou E, Arias MA, Reljic R (2009) TNF-alpha in tuberculosis: a cytokine with a split personality. Inflamm Allergy Drug Targets 8:53–62CrossRefGoogle Scholar
  15. Omae Y, Toyo-Oka L, Yanai H, Nedsuwan S, Wattanapokayakit S, Satproedprai N, Smittipat N, Palittapongarnpim P, Sawanpanyalert P, Inunchot W et al (2017) Pathogen lineage-based genome-wide association study identified CD53 as susceptible locus in tuberculosis. J Hum Genet 62:1015–1022CrossRefGoogle Scholar
  16. Parthasarathy V, Martin F, Higginbottom A, Murray H, Moseley GW, Read RC, Mal G, Hulme R, Monk PN, Partridge LJ (2009) Distinct roles for tetraspanins CD9, CD63 and CD81 in the formation of multinucleated giant cells. Immunology 127:237–248CrossRefGoogle Scholar
  17. Peters W, Ernst JD (2003) Mechanisms of cell recruitment in the immune response to Mycobacterium tuberculosis. Microbes Infect 5:151–158CrossRefGoogle Scholar
  18. Rabbee N, Speed TP (2006) A genotype calling algorithm for affymetrix SNP arrays. Bioinformatics 22:7–12CrossRefGoogle Scholar
  19. Seu L, Sun JJ, Schaaf KR, Duverger AE, Kutsch O, Goepfert PA (2016) The tetraspanin CD151 is an activation molecule that characterizes M. tuberculosis- specific effector CD4+ T cells. J Immunol 196:65.9Google Scholar
  20. Sobota RS, Stein CM, Kodaman N, Scheinfeldt LB, Maro I, Wieland-Alter W, Igo RP Jr, Magohe A, Malone LL, Chervenak K et al (2016) A locus at 5q33.3 confers resistance to tuberculosis in highly susceptible individuals. Am J Hum Genet 98:514–524CrossRefGoogle Scholar
  21. Thye T, Vannberg FO, Wong SH, Owusu-Dabo E, Osei I, Gyapong J, Sirugo G, Sisay-Joof F, Enimil A, Chinbuah MA et al (2010) Genome-wide association analyses identifies a susceptibility locus for tuberculosis on chromosome 18q11.2. Nat Genet 42:739–741CrossRefGoogle Scholar
  22. Thye T, Owusu-Dabo E, Vannberg FO, van Crevel R, Curtis J, Sahiratmadja E, Balabanova Y, Ehmen C, Muntau B, Ruge G et al (2012) Common variants at 11p13 are associated with susceptibility to tuberculosis. Nat Genet 44:257–259CrossRefGoogle Scholar
  23. Todros-Dawda I, Kveberg L, Vaage JT, Inngjerdingen M (2014) The tetraspanin CD53 modulates responses from activating NK cell receptors, promoting LFA-1 activation and dampening NK cell effector functions. PLoS One 9:e97844CrossRefGoogle Scholar
  24. van der Eijk EA, van de Vosse E, Vandenbroucke JP, van Dissel JT (2007) Heredity versus environment in tuberculosis in twins: the 1950s United Kingdom Prophit Survey Simonds and Comstock revisited. Am J Respir Crit Care Med 176:1281–1288CrossRefGoogle Scholar
  25. Wisdom R, Johnson RS, Moore C (1999) c-Jun regulates cell cycle progression and apoptosis by distinct mechanisms. EMBO J 18:188–197CrossRefGoogle Scholar
  26. Yunta M, Lazo PA (2003) Apoptosis protection and survival signal by the CD53 tetraspanin antigen. Oncogene 22:1219–1224CrossRefGoogle Scholar
  27. Yunta M, Oliva JL, Barcia R, Horejsi V, Angelisova P, Lazo PA (2002) Transient activation of the c-Jun N-terminal kinase (JNK) activity by ligation of the tetraspan CD53 antigen in different cell types. Eur J Biochem 269:1012–1021CrossRefGoogle Scholar
  28. Zhang W, Liu HT (2002) MAPK signal pathways in the regulation of cell proliferation in mammalian cells. Cell Res 12:9–18CrossRefGoogle Scholar

Copyright information

© The Genetics Society of Korea and Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Department of Biomedical Laboratory Science, College of Life and Health SciencesHoseo UniversityAsanSouth Korea
  2. 2.Department of Biomedical Laboratory ScienceDaegu Health CollegeDaeguSouth Korea

Personalised recommendations