Abstract
We examined a gene polymorphism of a novel Z-disc–related protein, myospryn (cardiomyopathy-associated 5). We focused on one haplotype block associated with a tag single nucleotide polymorphism (SNP) that covered 16 of 27 coding SNPs with linkage disequilibrium (minor allele frequency 0.413). Screening a myospryn polymorphism (K2906N) in a general health check-up of a rural Japanese population revealed an association with cardiac diseases (p=0.0082). In further analysis of the interaction between K2906N and cardiac function in patients, K2906N was associated with the anteroseptal wall thickness of the left ventricle in a recessive model (p=0.0324) and with the ratio of the peak velocity of the early diastolic filling wave to the peak velocity of atrial filling (A/E) (p=0.0278). In an association study based on left ventricular wall thickness, we found a significant difference in the K2906N genotype between controls and patients with cardiac hypertrophy. These results suggest that the K2906N polymorphism could be clinically associated with left ventricular hypertrophy and diastolic dysfunction independent of known parameters. Although the precise mechanism underlying this association remains to be elucidated, treatment with angiotensin II induced an increase in heart myospryn mRNA level in vitro and in vivo. Our results suggest that the polymorphism of myospryn is associated with left ventricular hypertrophy, and an association between a Z-disc protein and cardiac adaptation in response to pressure overload.
Similar content being viewed by others
Article PDF
References
Levy D, Anderson KM, Savage DD, et al: Echocardiographically detected left ventricular hypertrophy: prevalence and risk factors. The Framingham Heart Study. Ann Intern Med 1988; 108: 7–13.
Karjalainen J, Mantysaari M, Viitasalo M, Kujala U : Left ventricular mass, geometry, and filling in endurance athletes: association with exercise blood pressure. J Appl Physiol 1997; 82: 531–537.
Chien KR : Genomic circuits and the integrative biology of cardiac diseases. Nature 2000; 407: 227–232.
Csapo A, Erdos T, De Mattos CR, Gramss E, Moscowitz C : Stretch-induced uterine growth, protein synthesis and function. Nature 1965; 207: 1378–1379.
Sadoshima J, Xu Y, Slayter HS, Izumo S : Autocrine release of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro. Cell 1993; 75: 977–984.
Schunkert H, Hense HW, Holmer SR, et al: Association between a deletion polymorphism of the angiotensin-converting-enzyme gene and left ventricular hypertrophy. N Engl J Med 1994; 330: 1634–1638.
Osterop AP, Kofflard MJ, Sandkuijl LA, et al: AT1 receptor A/C1166 polymorphism contributes to cardiac hypertrophy in subjects with hypertrophic cardiomyopathy. Hypertension 1998; 32: 825–830.
Ruwhof C, van der Laarse A : Mechanical stress–induced cardiac hypertrophy: mechanisms and signal transduction pathways. Cardiovasc Res 2000; 47: 23–37.
Epstein ND, Davis JS : Sensing stretch is fundamental. Cell 2003; 112: 147–150.
Knoll R, Hoshijima M, Chien K : Cardiac mechanotransduction and implications for heart disease. J Mol Med 2003; 81: 750–756.
Olson TM, Michels VV, Thibodeau SN, Tai YS, Keating MT : Actin mutations in dilated cardiomyopathy, a heritable form of heart failure. Science 1998; 280: 750–752.
Arber S, Hunter JJ, Ross J, et al: MLP-deficient mice exhibit a disruption of cardiac cytoarchitectural organization, dilated cardiomyopathy, and heart failure. Cell 1997; 88: 393–403.
Gregorio CC, Trombitas K, Centner T, et al: The NH2 terminus of titin spans the Z-disc: its interaction with a novel 19-kD ligand (T-cap) is required for sarcomeric integrity. J Cell Biol 1998; 143: 1013–1027.
Moreira ES, Wiltshire TJ, Faulkner G, et al: Limb-girdle muscular dystrophy type 2G is caused by mutations in the gene encoding the sarcomeric protein telethonin. Nat Genet 2000; 24: 163–166.
Knoll R, Hoshijima M, Hoffman HM, et al: The cardiac mechanical stretch sensor machinery involves a Z disc complex that is defective in a subset of human dilated cardiomyopathy. Cell 2002; 111: 943–955.
Benson MA, Tinsley CL, Blake DJ : Myospryn is a novel binding partner for dysbindin in muscle. J Biol Chem 2004; 279: 10450–10458.
Durham JT, Brand OM, Arnold M, et al: Myospryn is a direct transcriptional target for MEF2A that encodes a striated muscle, alpha-actinin interacting, costamere localized protein. J Biol Chem 2006; 281: 6841–6849.
Fujiwara T, Saitoh S, Takagi S, et al: Prevalence of asymptomatic arteriosclerosis obliterans and its relationship with risk factors in inhabitants of rural communities in Japan: Tanno-Sobetsu study. Atherosclerosis 2004; 177: 83–88.
Devereux RB, Reichek N : Echocardiographic determination of left ventricular mass in man. Anatomic validation of the method. Circulation 1977; 55: 613–618.
Rakowski H, Appleton C, Chan KL, et al: Canadian consensus recommendations for the measurement and reporting of diastolic dysfunction by echocardiography: from the Investigators of Consensus on Diastolic Dysfunction by Echocardiography. J Am Soc Echocardiogr 1996; 9: 736–760.
Takemoto M, Node K, Nakagami H, et al: Statins as antioxidant therapy for preventing cardiac myocyte hypertrophy. J Clin Invest 2001; 108: 1429–1437.
Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP : Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med 1990; 322: 1561–1566.
Messerli FH : Antihypertensive therapy—going to the heart of the matter. Circulation 1990; 81: 1128–1135.
Ingber DE : Tensegrity I. Cell structure and hierarchical systems biology. J Cell Sci 2003; 116: 1157–1173.
Ingber DE : Tensegrity II. How structural networks influence cellular information processing networks. J Cell Sci 2003; 116: 1397–1408.
Vandenburgh H, Kaufman S : In vitro model for stretch-induced hypertrophy of skeletal muscle. Science 1979; 203: 265–268.
Komuro I, Kaida T, Shibazaki Y, et al: Stretching cardiac myocytes stimulates protooncogene expression. J Biol Chem 1990; 265: 3595–3598.
Ingber DE : Mechanical signaling and the cellular response to extracellular matrix in angiogenesis and cardiovascular physiology. Circ Res 2002; 91: 877–887.
Gerull B, Gramlich M, Atherton J, et al: Mutations of TTN, encoding the giant muscle filament titin, cause familial dilated cardiomyopathy. Nat Genet 2002; 30: 201–204.
Lee W, Hwang TH, Kimura A, et al: Different expressivity of a ventricular essential myosin light chain gene Ala57Gly mutation in familial hypertrophic cardiomyopathy. Am Heart J 2001; 141: 184–189.
Hayashi T, Arimura T, Ueda K, et al: Identification and functional analysis of a caveolin-3 mutation associated with familial hypertrophic cardiomyopathy. Biochem Biophys Res Commun 2004; 313: 178–184.
Pyle WG, Solaro RJ : At the crossroads of myocardial signaling: the role of Z-discs in intracellular signaling and cardiac function. Circ Res 2004; 94: 296–305.
Ervasti JM : Costameres: the Achilles' heel of Herculean muscle. J Biol Chem 2003; 278: 13591–13594.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Nakagami, H., Kikuchi, Y., Katsuya, T. et al. Gene Polymorphism of Myospryn (Cardiomyopathy-Associated 5) Is Associated with Left Ventricular Wall Thickness in Patients with Hypertension. Hypertens Res 30, 1239–1246 (2007). https://doi.org/10.1291/hypres.30.1239
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1291/hypres.30.1239
Keywords
This article is cited by
-
CMYA5 establishes cardiac dyad architecture and positioning
Nature Communications (2022)
-
Myospryn deficiency leads to impaired cardiac structure and function and schizophrenia-associated symptoms
Cell and Tissue Research (2021)
-
Association of four imprinting disorders and ART
Clinical Epigenetics (2019)
-
Ryanodine receptors are part of the myospryn complex in cardiac muscle
Scientific Reports (2017)
-
Role of common sarcomeric gene polymorphisms in genetic susceptibility to left ventricular dysfunction
Journal of Genetics (2016)