Abstract
Purpose
Recently, the roles of TIM-1 genetic polymorphisms in asthma have been extensively studied, with conflicting results. Therefore, we performed the present meta-analysis to better assess potential associations of TIM-1 genetic polymorphisms with asthma.
Methods
Eligible articles were searched in PubMed, Medline, EMBASE, Google Scholar, and CNKI up to December 2016. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to detect any potential associations between TIM-1 genetic polymorphisms and asthma.
Results
A total of 12 articles including 3120 asthma patients and 2825 control subjects were analyzed. The overall and subgroup analyses revealed that TIM-1-416G>C single nucleotide polymorphism was significantly associated with asthma for the Asian population in the codominant (G/G vs. G/C, p = 0.0003, OR 1.86, 95% CI 1.33–2.60) and dominant (G/G vs. G/C + C/C, p < 0.0001, OR 1.94, 95% CI 1.40–2.69) genetic models. Nevertheless, we failed to detect any significant associations between TIM-1-416G>C single nucleotide polymorphism and asthma in Caucasians. Additionally, according to our analyses, TIM-1 5383_5397 insertion/deletion polymorphism was not correlated with asthma in both Asians and Caucasians.
Conclusions
In conclusion, our findings suggest that TIM-1-416G>C single nucleotide polymorphism is associated with asthma susceptibility for the Asian ethnicity in certain genetic models. However, TIM-1 5383_5397 insertion/deletion polymorphism may not be correlated with the risk of asthma.
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References
Bousquet J, Humbert M (2015) GINA 2015: the latest iteration of a magnificent journey. Eur Respir J 46:579–582
Pawankar R, Canonica GW, Holgate ST, Lockey RF (2012) Allergic diseases and asthma: a major global health concern. Curr Opin Allergy Clin Immunol 12:39–41
Ober C, Yao TC (2011) The genetics of asthma and allergic disease: a 21st century perspective. Immunol Rev 242:10–30
Zhang Y, Moffatt MF, Cookson WO (2012) Genetic and genomic approaches to asthma: new insights for the origins. Curr Opin Pulm Med 18:6–13
Wills-Karp M, Ewart SL (2004) Time to draw breath: asthma susceptibility genes are identified. Nat Rev Genet 5:376–387
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 235:172–189
Khademi M, Illés Z, Gielen AW et al (2004) T Cell Ig- and mucin domain-containing molecule-3 (TIM-3) and TIM-1 molecules are differentially expressed on human Th1 and Th2 cells and in cerebrospinal fluid-derived mononuclear cells in multiple sclerosis. J Immunol 172:7169–7176
Meyers JH, Sabatos CA, Chakravarti S, Kuchroo VK (2005) The TIM gene family regulates autoimmune and allergic diseases. Trends Mol Med 11:362–369
Kuchroo VK, Umetsu DT, DeKruyff RH, Freeman GJ (2003) The TIM gene family: emerging roles in immunity and disease. Nat Rev Immunol 3:454–462
Chae SC, Song JH, Heo JC et al (2003) Molecular variations in the promoter and coding regions of human Tim-1 gene and their association in Koreans with asthma. Hum Immunol 64:1177–1182
Chen JP, Zhao WL, He NH et al (2012) Association of hepatitis A exposure and TIM-1 with childhood allergic asthma. J Asthma 49:697–702
Liu Q, Shang L, Li J et al (2007) A functional polymorphism in the TIM-1 gene is associated with asthma in a Chinese Han population. Int Arch Allergy Immunol 144:197–202
Mete F, Ozkaya E, Aras S et al (2014) Association between gene polymorphisms in TIM1, TSLP, IL18R1 and childhood asthma in Turkish population. Int J Clin Exp Med 7:1071–1077
Shirzade H, Meshkat R, Ganjalikhani-Hakemi M et al (2015) Association analysis of -416 G > C polymorphism of T-cell immunoglobulin and mucin domain-1 gene with asthma in Iran. Int J Immunogenet 42:265–269
Sinha S, Singh J, Jindal SK (2015) Protective association of TIM1-1454G>A Polymorphism with asthma in a North Indian population. Lung 193:31–38
Chae SC, Song JH, Lee YC et al (2003) The association of the exon 4 variations of Tim-1 gene with allergic diseases in a Korean population. Biochem Biophys Res Commun 312:346–350
Cui TP, Jin J, Liu CY et al (2004) Exploring the possibility of a relationship between polymorphism in TIM-1 and allergic asthma in children of the Hans from Hubei province of China. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 21:403–406
Gao PS, Mathias RA, Plunkett B 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 115:982–988
Li JS, Liu QJ, Wang P et al (2006) Absence of association between two insertion/deletion coding genetic polymorphisms of TIM-1 gene and asthma in Chinese Han population. Int J Immunogenet 33:417–422
Wu Q, Hu L, Cai P, Chen F, Kong L (2009) Association analysis of TIM-1-232G>A and 5383_5397 insertion/deletion polymorphisms with childhood asthma and total serum immunoglobulin E levels in middle China. J Investig Allergol Clin Immunol 19:146–153
Xu J, Jiang P, Liu J (2014) Pooled analysis of the association between TIM-1 5383_5397 insertion/deletion polymorphism and asthma susceptibility. Mol Biol Rep 41:7825–7831
Doull IJ, Lawrence S, Watson M et al (1996) Allelic association of gene markers on chromosomes 5q and 11q with atopy and bronchial hyperresponsiveness. Am J Respir Crit Care Med 153:1280–1284
Noguchi E, Shibasaki M, Arinami T, Takeda K, Maki T, Miyamoto T (1997) Evidence for linkage between asthma/atopy in childhood and chromosome 5q31-q33 in a Japanese population. Am J Respir Crit Care Med 156:1390–1393
Shek LP, Tay AH, Chew FT, Goh DL, Lee BW (2001) Genetic susceptibility to asthma and atopy among Chinese in Singapore-linkage to markers on chromosome 5q31-33. Allergy 56:749–753
Umetsu SE, Lee WL, McIntire JJ et al (2005) TIM-1 induces T cell activation and inhibits the development of peripheral tolerance. Nat Immunol 6:447–454
Acknowledgements
This work was supported by grants from the National Natural Science Foundation of China (81270289, 81300169).
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All analyses in the present meta-analysis were based on the previous published studies; thus, no ethical approval and patient consent are required.
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Xie, X., Shi, X., Chen, P. et al. Associations of TIM-1 Genetic Polymorphisms with Asthma: A Meta-analysis. Lung 195, 353–360 (2017). https://doi.org/10.1007/s00408-017-0006-5
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DOI: https://doi.org/10.1007/s00408-017-0006-5