Lung

, Volume 193, Issue 1, pp 31–38 | Cite as

Protective Association of TIM1−1454G>A Polymorphism with Asthma in a North Indian Population

  • Shweta Sinha
  • Jagtar Singh
  • Surinder Kumar Jindal
Article

Abstract

Purpose

TIM1 is a key regulator of Th2-dominated immune responses, including allergy, asthma, autoimmunity, and response to the pathogens. They are mainly expressed by hepatocytes and lymphoid cells. Analysis of the sequence of TIM1 was found to have range of SNPs which increases the transcriptional activity of the TIM1 gene.

Methods

A case–control study was conducted with a total of 964 subjects, including 483 healthy controls and 481 asthma patients in the present study. DNA samples were extracted from blood, and genotyping was done using polymerase chain reaction–restriction fragment length polymorphism method.

Results

Statistical analysis revealed that both heterozygous (GA) as well as the mutant (AA) genotype of −1454G>A (rs41297579) polymorphism shows resistance toward asthma with OR = 0.74, 95 % CI (0.55–0.98), p = 0.029 and OR = 0.43, 95 % CI (0.28–0.65), p = 0.000, respectively. The mutant (A) allele was also found to be highly protective toward asthma with OR = 0.68, 95 % CI (0.56–0.82) p = 0.000. However, no statistical difference was found between the TIM1–416G>C (rs9313422) polymorphism and asthma patients (p > 0.05).

Conclusions

This is the first study conducted in India conferring −1454G>A polymorphism provides resistance toward asthma while lack of association was found between −416G>C polymorphism and asthma in the studied North Indian population.

Keywords

Asthma North India TIM1 Polymorphisms PCR–RFLP Total IgE 

Notes

Acknowledgments

The authors thank the medical institute for their cooperation in allowing them to contact the patients and to obtain their detailed clinical information.

Conflict of interest

None.

References

  1. 1.
    Cavkaytar O, Sekerel BE (2014) Baseline management of asthma control. Allergol Immunopathol (Madr) 42(2):162–168. doi:10.1016/j.aller.2012.10.004
  2. 2.
    de Souza AJ, Oriss TB, O’malley KJ, Ray A, Kane LP (2005) T cell Ig and mucin 1 (TIM-1) is expressed on in vivo-activated T cells and provides a costimulatory signal for T cell activation. Proc Natl Acad Sci USA 102(47):17113–17118PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Freeman GJ, Casasnovas JM, Umetsu DT, DeKruyff RH (2010) TIM genes: a family of cell surface phosphatidylserine receptors that regulate innate and adaptive immunity. Immunol Rev 235(1):172–189. doi:10.1111/j.0105-2896.2010.00903.x PubMedCentralPubMedGoogle Scholar
  4. 4.
    McIntire JJ, Umetsu DT, DeKruyff RH (2004) TIM-1, a novel allergy and asthma susceptibility gene. Springer Semin Immunopathol 25(3–4):335–348PubMedCrossRefGoogle Scholar
  5. 5.
    Umetsu SE, Lee WL, McIntire JJ, Downey L, Sanjanwala B et al (2005) TIM-1 induces T cell activation and inhibits the development of peripheral tolerance. Nat Immunol 6(5):447–454PubMedCrossRefGoogle Scholar
  6. 6.
    Rodriguez-Manzanet R, DeKruyff R, Kuchroo VK, Umetsu DT (2009) The costimulatory role of TIM molecules. Immunol Rev 229(1):259–270PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Curtiss ML, Gorman JV, Businga TR, Traver G, Singh M et al (2012) TIM-1 regulates Th2 responses in airway hypersensitivity model. Eur J Immunol 42(3):651–661. doi:10.1002/eji.201141581 PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    McIntire JJ, Umetsu SE, Macaubas C, Hoyte EG, Cinnioglu C et al (2003) Immunology: hepatitis A virus link to atopic disease. Nature 425(6958):576PubMedCrossRefGoogle Scholar
  9. 9.
    Nakajima T, Wooding S, Satta Y, Jinnai N, Goto S, Hayasaka I et al (2005) Evidence for natural selection in the HAVCR1 gene: high degree of amino-acid variability in the mucin domain of human HAVCR1 protein. Genes Immun 6(5):398–406PubMedCrossRefGoogle Scholar
  10. 10.
    Kuchroo VK, Umetsu DT, DeKruyff RH, Freeman GJ (2003) The TIM gene family: emerging roles in immunity and disease. Nat Rev Immunol 3:454–462PubMedCrossRefGoogle Scholar
  11. 11.
    Graves PE, Siroux V, Guerra S, Klimecki WT, Martinez FD (2005) Association of atopy and eczema with polymorphisms in T-cell immunoglobulin domain and mucin domain-IL-2-inducible T-cell kinase gene cluster in chromosome 5 q 33. J Allergy Clin Immunol 116(3):650–656PubMedCrossRefGoogle Scholar
  12. 12.
    Gao PS, Mathias RA, Plunkett B, Togias A, Barnes KC, Beaty TH et al (2005) Genetic variants of the T-cell immunoglobulin mucin 1 but not the T-cell immunoglobulin mucin 3 gene are associated with asthma in an African American population. J Allergy Clin Immunol 115(5):982–988PubMedCrossRefGoogle Scholar
  13. 13.
    Mou Z, Shi J, Tan Y, Xu R, Zhao Z, Xu G, Li H (2010) Association between TIM-1 gene polymorphisms and allergic rhinitis in a Han Chinese population. J Investig Allergol Clin Immunol 20:3–8PubMedGoogle Scholar
  14. 14.
    Liu Q, Shang L, Li J, Wang P, Li H, Wei C, Gong Y (2007) A functional polymorphism in the TIM-1 gene is associated with asthma in a Chinese Han population. Int Arch Allergy Immunol 144(3):197–202PubMedCrossRefGoogle Scholar
  15. 15.
    Rathod VPS, Kapoor P, Pillai KK, Khanam R (2010) Assessment of asthma and chronic obstructive pulmonary disorder in relation to reversibility, IgE, eosinophil, and neutrophil count in a university teaching hospital in South Delhi, India. J Pharm Bioallied Sci 2(4):337–340. doi:10.4103/0975-7406.72136 PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Miller MR, Hankinson J, Brusasco V et al (2005) Standardisation of spirometry. ATS/ERS Task Force. Eur Respir J 26(2):319–338PubMedCrossRefGoogle Scholar
  17. 17.
    Przybilla B, Ring J, Volk M (1986) Total IgE levels in the serum in dermatologic diseases. Hautarzt 37(2):77–82PubMedGoogle Scholar
  18. 18.
    Roe BA, Crabtree JS, Khan AS (1996) DNA isolation and sequencing. In: Rickwood D (ed) Essential techniques series, Wiley, New York, pp 85–86, 116–117Google Scholar
  19. 19.
    Xu JR, Yang Y, Liu XM, Sun JY, Wang YJ (2012) Polymorphisms of the TIM-1 gene are associated with rheumatoid arthritis in the Chinese Hui minority ethnic population. Genet Mol Res 11(1):61–69. doi:10.4238/2012 PubMedCrossRefGoogle Scholar
  20. 20.
    Bosnjak B, Stelzmueller B, Erb KJ, Epstein MM (2011) Treatment of allergic asthma: modulation of Th2 cells and their responses. Respir Res 12(1):114. doi:10.1186/1465-9921-12-114 PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    McIntire JJ, Umetsu SE, Akbari O, Potter M, Kuchroo VK, Barsh GS et al (2001) Identification of Tapr (an airway hyperreactivity regulatory locus) and the linked TIM gene family. Nat Immunol 2(12):1109–1116PubMedCrossRefGoogle Scholar
  22. 22.
    Encinas JA, Janssen EM, Weiner DB, Calarota SA, Nieto D, Moll T et al (2005) Anti-T-cell Ig and mucin domain-containing protein 1 antibody decreases TH2 airway inflammation in a mouse model of asthma. J Allergy Clin Immunol 116(6):1343–1349PubMedCrossRefGoogle Scholar
  23. 23.
    Sizing ID, Bailly V, McCoon P, Chang W, Rao S, Pablo L et al (2007) Epitope-dependent effect of anti-murine TIM-1 monoclonal antibodies on T cell activity and lung immune responses. J Immunol 178(4):2249–2261PubMedCrossRefGoogle Scholar
  24. 24.
    Christodoulopoulos P, Cameron L, Nakamura Y, Lemiere C, Muro S et al (2001) Th2 cytokine-associated transcription factors in atopic and nonatopic asthma: evidence for differential signal transducer and activator of transcription 6 expression. J Allergy Clin Immunol 107(4):586–591PubMedCrossRefGoogle Scholar
  25. 25.
    Erpenbeck VJ, Hagenberg A, Krentel H, Discher M, Braun A (2006) Regulation of GATA-3, c-maf and T-bet mRNA expression in bronchoalveolar lavage cells and bronchial biopsies after segmental allergen challenge. Int Arch Allergy Immunol 139(4):306–316PubMedCrossRefGoogle Scholar
  26. 26.
    Xu G, Cheng L, Lu L, Zhu Y, Xu R, Yao X, Li H (2008) Expression of T-cell immunoglobulin and mucin-domain-containing molecule-1 (TIM-1) is increased in a mouse model of asthma and relationship to GATA-3. Life Sci 82(11–12):663–669. doi:10.1016/j.lfs.2007.12.017 PubMedCrossRefGoogle Scholar
  27. 27.
    Lee J, Phong B, Egloff AM, Kane LP (2011) TIM polymorphisms—genetics and function. Genes Immun 12(8):595–604. doi:10.1038/gene.2011.75 PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Chae SC, Song JH, Heo JC, Lee YC, Kim JW, Chung HT (2003) Molecular variations in the promoter and coding regions of human TIM-1 gene and their association in Koreans with asthma. Hum Immunol 64(12):1177–1182PubMedCrossRefGoogle Scholar
  29. 29.
    Chen JP, Zhao WL, He NH, Gui Q, Xiong JP, Zhou HM et al (2012) Association of hepatitis A exposure and TIM-1 with childhood allergic asthma. J Asthma 49(7):697–702. doi:10.3109/02770903.2012.694539 PubMedCrossRefGoogle Scholar
  30. 30.
    Mete F, Ozkaya E, Aras S, Koksal V, Etlik O, Baris I (2014) Association between gene polymorphisms in TIM1, TSLP, IL18R1 and childhood asthma in Turkish population. Int J Clin Exp Med 7(4):1071–1077PubMedCentralPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Shweta Sinha
    • 1
  • Jagtar Singh
    • 1
  • Surinder Kumar Jindal
    • 2
  1. 1.Department of BiotechnologyPanjab UniversityChandigarhIndia
  2. 2.Department of Pulmonary MedicinePGIMERChandigarhIndia

Personalised recommendations