Abstract
Objective
The gene for mast cell chymase (CMA1) is an ideal candidate for investigating the genetic predisposition to coronary heart disease (CHD), as activated mast cells have been found to be present in a greater proportion in the shoulder region of atheroma than in normal coronary intimae. Previous studies have indicated that CMA1 promoter polymorphism rs1800875 may be involved in regulating immunoglobulin E (IgE) levels in patients with eczema, and it is associated with the progression of immunoglobulin A nephropathy.
Methods
The association between single nucleotide polymorphism (SNP) rs1800875, serum chymase, and serum IgE levels was examined in 175 CHD subjects and 95 non-CHD subjects.
Results
Statistical analysis indicated no significant difference in allele frequency between CHD and non-CHD. However, a significant association was found between CMA1 genotypes and total IgE levels in CHD subjects. Meanwhile, crossover analysis revealed that, in GG homozygotes, CHD risk was nearly six times higher in those with IgE (U/ml) level <2.58 (natural logarithm conversion), while no association was found with chymase level.
Conclusions
Polymorphism rs1800875 of CMA1 may be associated with serum IgE level in CHD subjects, but not with chymase level in both groups. In GG homozygotes, high IgE level is a protective factor against coronary disease.
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References
Busse, W.W., Lemanske, R.F., 2001. Advances in immunology: asthma. N. Engl. J. Med., 2001(344):350–362.
Criqui, M.H., Lee, E.R., Hamburger, R.N., Klauber, M.R., Coughlin, S.S., 1987. IgE and cardiovascular disease. Results from a population-based study. Am. J. Med., 82(5):964–968. [doi:10.1016/0002-9343(87)90159-8]
Galli, S.J., Kalesnikoff, J., Grimbaldeston, M.A., Piliponsky, A.M., Williams, C.M.M., Tsai, M., 2005. Mast cells as “tunable” effector and immunoregulatory cells: recent advances. Annu. Rev. Immunol., 23(1):749–786. [doi:10.1146/annurev.immunol.21.120601.141025]
Gardemann, A., Harnami, M., Katz, N., Tillmann, H., Haberbosch, W., 2000. The chyrnase A(-1903)G gene polymorphism is not associated with the risk and extent of coronary heart disease. Atherosclerosis, 150(2):445–446. [doi:10.1016/S0021-9150(00)00387-7]
Gurish, M.F., Austen, K.F., 2001. The diverse roles of mast cells. J. Exp. Med., 194(1):F1–F6. [doi:10.1084/jem.194.1.F1]
He, H., Li, L.M., Cao, W.H., Sun, N.L., liu, M.Z., Hu, Y.H., 2004. Association between the I/D polymorphism of the ACE gene, A/B polymorphism of the chymase gene and the left ventricular hypertrophy in essential hypertension. Chin. J. Hypertens., 12(1):39–43 (in Chinese).
Heikkila, H.M., Latti, S., Leskinen, M.J., Hakala, J.K., Kovanen, P.T., Lindstedt, K.A., 2008. Activated mast cells induce endothelial cell apoptosis by a combined action of chymase and tumor necrosis factor-α. Arterioscler. Thromb. Vasc. Biol., 28(2):309–314. [doi:10.1161/ATVBAHA.107.151340]
Ihara, M., Urata, H., Kinoshita, A., Suzumiya, J., Sasaguri, M., Kikuchi, M., Ideishi, M., Arakawa, K., 1999. Increased chymase-dependent angiotensin II formation in human atherosclerotic aorta. Hypertension, 33(6):1399–1405.
Imada, T., Komorita, N., Kobayashi, F., Naito, K., Yoshikawa, T., Miyazaki, M., Nakamura, N., Kondo, T., 2002. Therapeutic potential of a specific chymase inhibitor in atopic dermatitis. Jpn. J. Pharmacol., 90(3):214–217. [doi:10.1254/jjp.90.214]
Iwanaga, T., McEuen, A., Walls, A.F., Clough, J.B., Keith, T.P., Rorke, S., Barton, S.J., Holgate, S.T., Holloway, J.W., 2004. Polymorphism of the mast cell chymase gene (CMA1) promoter region: lack of association with asthma but association with serum total immunoglobulin E levels in adult atopic dermatitis. Clin. Exp. Allergy, 34(7): 1037–1042. [doi:10.1111/j.1365-2222.2004.02000.x]
Jeziorska, M., McCollum, C., Woolley, D.E., 1997. Mast cell distribution, activation, and phenotype in atherosclerotic lesions of human carotid arteries. J. Pathol., 182(1): 115–122. [doi:10.1002/(SICI)1096-9896(199705)182:1〈115::AID-PA TH806〉3.0.CO;2-9]
Korkmaz, M.E., Oto, A., Saraclar, Y., Oram, E., Oram, A., Ugurlu, S., Karamehmetoglu, A., Karaagaoglu, E., 1991. Levels of IgE in the serum of patients with coronary arterial disease. Int. J. Cardiol., 31(2):199–204. [doi:10.1016/0167-5273(91)90216-C]
Liang, Y.H., Chen, X.L., Yu, Z.S., Chen, C.Y., Bi, S., Mao, L.G., Zhou, B.L., Zhang, X.N., 2009. Deletion analysis of SMN1 and NAIP genes in southern Chinese children with spinal muscular atrophy. J. Zhejiang Univ.-Sci. B, 10(1): 29–34. [doi:10.1631/jzus.B0820125]
Longley, B.J., Tyrrell, L., Ma, Y., Williams, D.A., Halaban, R., Langley, K., Lu, H.S., Schechter, N.M., 1997. Chymase cleavage of stem cell factor yields a bioactive, soluble product. PNAS, 94(17):9017–9021. [doi:10.1073/pnas.94.17.9017]
Mizutani, H., Schechter, N., Lazarus, G., Black, R.A., Kupper, T.S., 1991. Rapid and specific conversion of precursor interleukin 1 β (IL-1β) to an active IL-1 species by human mast cell chymase. J. Exp. Med., 174(4):821–825. [doi:10.1084/jem.174.4.821]
Ortlepp, J.R., Janssens, U., Bleckmann, F., Lauscher, J., Merkelbach-Bruse, S., Hanrath, P., Hoffmann, R., 2001. A chymase gene variant is associated with atherosclerosis in venous coronary artery bypass grafts. Coron. Artery Dis., 12(6):493–497. [doi:10.1097/00019501-200109000-00008]
Pfeufer, A., Busjahn, A., Vergopoulos, A., Knoblauch, H., Urata, H., Osterziel, K.J., Menz, M., Wienker, T.F., Faulhaber, H.D., Steinmetz, A., et al., 1998. Chymase gene locus is not associated with myocardial infarction and is not linked to heart size or blood pressure. Am. J. Cardiol., 82(8):979–981. [doi:10.1016/S0002-9149(98)00518-9]
Qin, Y., Shi, G.P., 2011. Cysteinyl cathepsins and mast cell proteases in the pathogenesis and therapeutics of cardiovascular diseases. Pharmacol. Ther., 131(3):338–350. [doi:10.1016/j.pharmthera.2011.04.010]
Roselaar, S.E., Kakkanathu, P.X., Daugherty, A., 1996. Lymphocyte populations in atherosclerotic lesions of apoE −/− and LDL receptor −/− mice. Decreasing density with disease progression. Arterioscler. Thromb. Vasc. Biol., 16(8):1013–1018. [doi:10.1161/01.ATV.16.8.1013]
Schwartz, L.B., Austen, K.F., 1980. Enzymes of the mast cell granule. J. Invest. Dermatol., 74(5):349–353. [doi:10.1111/1523-1747.ep12543620]
Sharma, S., Rajan, U.M., Kumar, A., Soni, A., Ghosh, B., 2005. A novel (TG)n(GA)m repeat polymorphism 254 bp downstream of the mast cell chymase (CMA1) gene is associated with atopic asthma and total serum IgE levels. J. Hum. Genet., 50(6):276–282. [doi:10.1007/s10038-005-0252-x]
Sun, J., Sukhova, G.K., Wolters, P.J., Yang, M., Kitamoto, S., Libby, P., MacFarlane, L.A., Mallen-St Clair, J., Shi, G.P., 2007. Mast cells promote atherosclerosis by releasing proinflammatory cytokines. Nat. Med., 13(6):719–724. [doi:10.1038/nm1601]
Szczeklik, A., Nizankowski, R., Mruk, J., 1977. Myocardial infarction in status asthmaticus. Lancet, 1(8012):658–659. [doi:10.1016/S0140-6736(77)92102-X]
Szczeklik, A., Milner, P.C., Birch, J., Watkins, J., Martin, J.F., 1986. Prolonged bleeding time, reduced platelet aggregation, altered PAF-acether sensitivity and increased platelet mass are a trait of asthma and hay fever. Thromb. Haemost., 56(3):283–287.
Szczeklik, A., Sladek, K., Szczerba, A., Dropinski, J., 1988. Serum immunoglobulin E response to myocardial infarction. Circulation, 77(6):1245–1249. [doi:10.1161/01.CIR.77.6.1245]
Szczeklik, A., Dropinski, J., Gora, P.F., 1993. Serum immunoglobulin E and sudden cardiac arrest during myocardial infarction. Coron. Artery Dis., 4(11):1029–1032. [doi:10.1097/00019501-199311000-00012]
Tunon de Lara, J.M., Okayama, Y., McEuen, A.R., Heusser, C.H., Church, M.K., Walls, A.F., 1994. Release and inactivation of interleukin-4 by mast cells. Ann. N. Y. Acad. Sci., 725:50–58. [doi:10.1111/j.1749-6632.1994.tb39789.x]
Urata, H., Kinoshita, A., Perez, D.M., Misono, K.S., Bumpus, F.M., Graham, R.M., Husain, A., 1991. Cloning of the gene and cDNA for human heart chymase. J. Biol. Chem., 266(26):17173–17179.
Vercelli, D., 2008. Discovering susceptibility genes for asthma and allergy. Nat. Rev. Immunol., 8(3):169–182. [doi:10.1038/nri2257]
Wu, G.R., Ma, A.Q., Li, Z.H., Geng, T., 2002. Study of the association of the I/D polymorphism of the ACE gene, A/G polymorphism of the heart chymase gene and idiopathetic dilated cardiomyopathy. J. Clin. Cardiol., 18(3): 100–103 (in Chinese).
Xiang, M., Sun, J., Lin, Y., Zhang, J., Chen, H., Yang, D., Wang, J., Shi, G.P., 2011. Usefulness of serum tryptase level as an independent biomarker for coronary plaque instability in a Chinese population. Atherosclerosis, 215(2):494–499. [doi:10.1016/j.atherosclerosis.2011.01.006]
Xu, J., Postma, D.S., Howard, T.D., Koppelman, G.H., Zheng, S.L., Stine, O.C., Bleecker, E.R., Meyers, D.A., 2000. Major genes regulating total serum immunoglobulin E levels in families with asthma. Am. J. Hum. Genet., 67(5): 1163–1173. [doi:10.1086/321190]
Ying, S.Q., Xiang, M.X., Fang, L., Wang, J.A., 2010. Temporal changes in circulating P-selectin, plasminogen activator inhibitor-1, magnesium, and creatine kinase after percutaneous coronary intervention. J. Zhejiang Univ.-Sci. B, 11(8):575–582. [doi:10.1631/jzus.B1001006]
Yoshikawa, T., Imada, T., Nakakubo, H., Nakamura, N., Naito, K., 2001. Rat mast cell protease-I enhances immunoglobulin E production by mouse B cells stimulated with interleukin-4. Immunology, 104(3):333–340. [doi:10.1046/j.1365-2567.2001.01320.x]
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Project supported by the National Natural Science Foundation of China (No. 30670867) to Mei-xiang XIANG, and the Major Program of Science and Technology Department of Zhejiang Province, China (No. 2007C13058) to Mei-xiang XIANG
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Jin, Cn., Ma, H., Lin, Y. et al. Association between SNP rs1800875, serum chymase and immunoglobulin E levels in patients with coronary heart disease. J. Zhejiang Univ. Sci. B 12, 660–667 (2011). https://doi.org/10.1631/jzus.B1101008
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DOI: https://doi.org/10.1631/jzus.B1101008