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
March ME, Sleiman PMA, Hakonarson H (2013) Genetic polymorphisms and associated susceptibility to asthma. Int J Gen Med 6:253–265
Smith KR (2002) Indoor air pollution in developing countries: recommendations for research. Int J Indoor Environ Health 12:1–7
Pruss-Ustun A, Corvalan C (2006) Preventing disease through health environments. Towards an estimate of the environmental burden of disease, World Health Organisation
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
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
Debono M, Gordee RS (1994) Antibiotics that inhibit fungal cell wall development. Annu Rev Microbiol 48:471–497
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
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
Kanneganti M, Kamba A, Mizoguchi E (2012) Role of chitotriosidase (chitinase1) under normal and disease conditions. J Epithel Biol Pharmacol 5:1–9
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
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
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
Boot RG, Renkema GH, Verhoek M et al (1998) The human chitotriosidase gene. Nature of inherited enzyme deficiency. J Biol Chem 273:25680
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
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
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
Altarescu G, Rudensky B, Abrahamov A et al (2002) Plasma chitotriosidase activity in patients with beta-thalassemia. Am J Hematol 71(1):7–10
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
Comabella M, Domınguez C, Rio J et al (2009) Plasma chitotriosidase activity in multiple sclerosis. Clin Immunol 131:216–222
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
Miller MR, Hankinson J, Brusasco V et al (2005) Standardisation of spirometry. ATS/ERS Task Force. Eur Respir J 26(2):319–338
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
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
Barnes PJ (2008) The cytokine network in asthma and chronic obstructive pulmonary disease. J Clin Invest 118(11):3546–3556. doi:10.1172/JCI36130
McKenzie AN (2000) Regulation of T helper type 2 cell immunity by interleukin-4 and interleukin-13. Pharmacol Ther 88:143–151
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
Vicencio AG, Chupp GL, Tsirilakis K et al (2010) CHIT1 mutations: genetic risk factor for severe asthma with fungal sensitization? Pediatrics 126:e982
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
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
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
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
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
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
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
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.
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The authors declare that they have no conflict of interest.
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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