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Association of 24 bp Duplication of Human CHIT1 Gene with Asthma in a Heterozygous Population of North India: A Case–Control Study

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Abstract

Purpose

CHIT1 is expressed by pulmonary macrophages, which is typically the site of entry for many environmental fungi that may increase the risk of pulmonary fungal infection and lead to hypersensitivity. The conserved expression of this gene in humans suggests its physiological importance in the mammalian lung.

Methods

The present study was conducted with a total of 964 subjects, including 483 healthy controls and 481 asthma patients. DNA samples were extracted from blood, and the genotyping was done using polymerase chain reaction method.

Results

Statistical analysis revealed that the 24 bp duplication in CHIT1 gene polymorphism shows highly significant association in heterozygous (wild/dup) genotype with OR 1.74, 95 % CI (1.29–2.36), and p = 0.000. However, the homozygous mutant genotype (dup/dup) was found to be non-significant with OR 1.06, 95 % CI (0.69–1.63), and p = 0.786. The combination of both wild/dup and dup/dup was also found to be highly significant with OR 1.57, 95 % CI (1.18–2.11), and p = 0.002.

Conclusions

This is the first study conducted in India which reports a significant association between 24 bp duplication in CHIT1 gene polymorphism and asthma in the studied North Indian population.

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References

  1. March ME, Sleiman PMA, Hakonarson H (2013) Genetic polymorphisms and associated susceptibility to asthma. Int J Gen Med 6:253–265

    PubMed Central  PubMed  Google Scholar 

  2. Smith KR (2002) Indoor air pollution in developing countries: recommendations for research. Int J Indoor Environ Health 12:1–7

    Google Scholar 

  3. Pruss-Ustun A, Corvalan C (2006) Preventing disease through health environments. Towards an estimate of the environmental burden of disease, World Health Organisation

    Google Scholar 

  4. Juarez-Rendon KJ, Lara-Aguilar RA, Garcia-Ortiz JE (2012) 24-bp duplication on CHIT1 gene in Mexican population. Rev Med Inst Mex Seguro Soc 50(4):375–377

    PubMed  Google Scholar 

  5. Araujo AC, Souto-Padron T, de Souza W (1993) Cytochemical localization of carbohydrate residues in microfilariae of Wuchereria bancrofti and Brugia malayi. J Histochem Cytochem 41:571–578

    Article  CAS  PubMed  Google Scholar 

  6. Debono M, Gordee RS (1994) Antibiotics that inhibit fungal cell wall development. Annu Rev Microbiol 48:471–497

    Article  CAS  PubMed  Google Scholar 

  7. Elias JA, Homer RJ, Hamid Q, Lee CG (2005) Chitinases and chitinase-like proteins in T(H)2 inflammation and asthma. J Allergy Clin Immunol 116(3):497–500

    Article  CAS  PubMed  Google Scholar 

  8. Tachu B, Pillai S, Lucius R, Pogonka T (2008) Essential role of chitinase in the development of the filarial nematode Acanthocheilonema viteae. Infect Immun 76(1):221–228

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Kanneganti M, Kamba A, Mizoguchi E (2012) Role of chitotriosidase (chitinase1) under normal and disease conditions. J Epithel Biol Pharmacol 5:1–9

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Malaguarnera L, Musumeci M, Di Rosa M, Scuto A, Musumeci S (2005) Interferon-γ, tumor necrosis factor-α, and lipopolysaccharide promote chitotriosidase gene expression in human macrophages. J Clin Lab Anal 19(3):128–132

    Article  CAS  PubMed  Google Scholar 

  11. van Eijk M, van Roomen CP, Renkema GH et al (2005) Characterization of human phagocyte-derived chitotriosidase, a component of innate immunity. Int Immunol 17:1505–1512

    Article  PubMed  Google Scholar 

  12. Di Rosa M, Malaguarnera G, De Gregorio C, D’Amico F, Mazzarino MC, Malaguarnera L (2013) Modulation of chitotriosidase during macrophage differentiation. Cell Biochem Biophys 66(2):239–247. doi:10.1007/s12013-012-9471-x

    Article  CAS  PubMed  Google Scholar 

  13. Boot RG, Renkema GH, Verhoek M et al (1998) The human chitotriosidase gene. Nature of inherited enzyme deficiency. J Biol Chem 273:25680

    Article  CAS  PubMed  Google Scholar 

  14. Canudas J, Cenarro A, Civeira F et al (2001) Chitotriosidase genotype and serum activity in subjects with combined hyperlipidemia: effect of the lipid-lowering agents, atorvastatin and bezafibrate. Metabolism 50:447–450

    Article  CAS  PubMed  Google Scholar 

  15. Malaguarnera L, Simpore J, Prodi DA et al (2003) A 24-bp duplication in exon ten of human chitotriosidase gene from the sub-Saharan to the Mediterranean area: role of parasitic diseases and environmental conditions. Genes Immun 4:570–574

    Article  CAS  PubMed  Google Scholar 

  16. Brinkman J, Wijburg FA, Hollak CE, Groener JE, Verhoek M (2005) Plasma chitotriosidase and CCL18: early biochemical surrogate markers in type B Niemann-Pick disease. J Inherit Metab Dis 28:13–20

    Article  CAS  PubMed  Google Scholar 

  17. Altarescu G, Rudensky B, Abrahamov A et al (2002) Plasma chitotriosidase activity in patients with beta-thalassemia. Am J Hematol 71(1):7–10

    Article  CAS  PubMed  Google Scholar 

  18. Boot RG, Hollak CE, Verhoek M et al. (2010) Plasma chitotriosidase and CCL18 as surrogate markers for granulomatous macrophages in sarcoidosis. Clin Chim Acta 411(1–2):31–36. doi: 10.1016/j.cca.2009.09.034. Epub 2009 Oct 4

  19. Comabella M, Domınguez C, Rio J et al (2009) Plasma chitotriosidase activity in multiple sclerosis. Clin Immunol 131:216–222

    Article  CAS  PubMed  Google Scholar 

  20. Karadag B, Kucur M, Isman FK, Hacibekiroglu M, Vural VA (2008) Serum chitotriosidase activity in patients with coronary artery disease. Circ J 72(1):71–75

    Article  CAS  PubMed  Google Scholar 

  21. Miller MR, Hankinson J, Brusasco V et al (2005) Standardisation of spirometry. ATS/ERS Task Force. Eur Respir J 26(2):319–338

    Article  CAS  PubMed  Google Scholar 

  22. Roe BA, Crabtree JS, Khan AS (1996) DNA isolation and sequencing.In: Rickwood D (ed) Essential techniques series, John Wiley and Sons, New York, p 85–86, 116–117

  23. Ales M, Igor M, Barbara S, Marjeta Z, Borut P (2010) The role of chitotriosidase duplication gene polymorphism in the susceptibility to sarcoidosis. Zdr Vestn 79:837–842

    Google Scholar 

  24. Barnes PJ (2008) The cytokine network in asthma and chronic obstructive pulmonary disease. J Clin Invest 118(11):3546–3556. doi:10.1172/JCI36130

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. McKenzie AN (2000) Regulation of T helper type 2 cell immunity by interleukin-4 and interleukin-13. Pharmacol Ther 88:143–151

    Article  CAS  PubMed  Google Scholar 

  26. Sutherland TE, Maizels RM, Allen JE (2009) Chitinases and chitinase-like proteins: potential therapeutic targets for the treatment of T-helper type 2 allergies. Clin Exp Allergy 39(7):943–955. doi:10.1111/j.1365-2222.2009.03243.x

    Article  CAS  PubMed  Google Scholar 

  27. Vicencio AG, Chupp GL, Tsirilakis K et al (2010) CHIT1 mutations: genetic risk factor for severe asthma with fungal sensitization? Pediatrics 126:e982

    Article  PubMed  Google Scholar 

  28. Zimmermann N, King NE, Laporte J et al (2003) Dissection of experimental asthma with DNA microarray analysis identifies arginase in asthma pathogenesis. J Clin Invest 111(12):1863–1874

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Zhu Z, Zheng T, Homer RJ et al (2004) Acidic mammalian chitinase in asthmatic Th2 inflammation and IL-13 pathway activation. Science 304(5677):1678–1682

    Article  CAS  PubMed  Google Scholar 

  30. Zhao J, Zhu H, Wong CH, Leung KY, Wong WS (2005) Increased lungkine and chitinase levels in allergic airway inflammation: a proteomics approach. Proteomics 5(11):2799–2807

    Article  CAS  PubMed  Google Scholar 

  31. Wu AC, Lasky-Su J, Rogers CA, Klanderman BJ, Litonjua AA (2010) Fungal exposure modulates the effect of polymorphisms of chitinases on emergency department visits and hospitalizations. Am J Respir Crit Care Med 182(7):884–889

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Bierbaum S, Superti-Furga A, Heinzmann A (2006) Genetic polymorphisms of chitotriosidase in Caucasian children with bronchial asthma. Int J Immunogenet 33:201–204. doi:10.1111/j.1744-313X.2006.00597.x

    Article  CAS  PubMed  Google Scholar 

  33. Lee CG, Da Silva CA, Lee JY, Hartl D, Elias JA (2008) Chitin regulation of immune responses: an old molecule with new roles. Curr Opin Immunol 20(6):684–689. doi:10.1016/j.coi.2008.10.002

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Ohno M, Togashi Y, Tsuda K et al (2013) Quantification of chitinase mRNA levels in human and mouse tissues by real-time PCR: species-specific expression of acidic mammalian chitinase in stomach tissues. PLoS ONE 8(6):e67399. doi:10.1371/journal.pone.0067399

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Acknowledgment

J. Singh is highly grateful to the Department of Science & Technology, New Delhi under the Ministry of Science & Technology, India, for providing research Grant (SR/FT/LS-018/2008) for the study.

Conflict of interest

The authors declare that they have no conflict of interest.

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Correspondence to Jagtar Singh.

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Sinha, S., Singh, J., Jindal, S.K. et al. Association of 24 bp Duplication of Human CHIT1 Gene with Asthma in a Heterozygous Population of North India: A Case–Control Study. Lung 192, 685–691 (2014). https://doi.org/10.1007/s00408-014-9605-6

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  • DOI: https://doi.org/10.1007/s00408-014-9605-6

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