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TGF-beta 1 Codon 10 Polymorphism is Associated with Cerebral SVD

Published online by Cambridge University Press:  02 December 2014

Hong-miao Tao*
School of Medicine, Jinhua College of Profession & Technology
Guo-zhong Chen
School of Medicine, Jinhua College of Profession & Technology
Xiao-dong Lu
Department of Clinical Laboratory, Jinhua Central Hospital
Xiao-gang Hu
Department of Radiology, Jinhua Central Hospital
Gan-ping Chen
Department of Neurology, Jinhua People's Hospital, Jinhua
Bei Shao
Cerebrovascular Unit, Department of Neurology, the First Affiliated Hospital, Wenzhou Medical College, Wenzhou, Zhejiang Province, the People's Republic of China
School of Medicine, Jinhua College of Profession & Technology, Jinhua, 321007, Zhejiang Province, The People's Republic of China.
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To clarify the role of inflammation in the pathogenesis of cerebral small vessel disease (SVD), we investigated whether the gene encoding transforming growth factor-beta 1(TGF-beta 1) is a risk factor for cerebral SVD as a whole, and for two different SVD subtypes.


TGF-beta 1 codon10 (T+29C) genotype was determined in 441 Chinese patients (313 male and 128 female) with cerebral SVD and 450 control subjects (326 male and 124 female). Cerebral SVD patients were retrospectively classified into two groups based on neuroimaging findings: lacunar infarction group with 112 patients and ischaemic leukoaraiosis group with 329 patients.


Subjects carrying TT homozygote were susceptible to cerebral SVD [adjusted odds ratio (OR) =1.44, 95% confidence interval (CI), 1.05-1.98; P=0.026]. Further analysis of SVD subtypes revealed a moderate association with the ischaemic leukoaraiosis group [OR= 1.60, 95% CI, 1.14-2.25; P=0.007].


Codon 10 of TGF-beta 1 might be a risk factor for SVD, specifically in ischaemic leukoaraiosis phenotype.

Original Articles
Copyright © The Canadian Journal of Neurological 2011


1.Erkinjuntti, T, Kurz, A, Gauthier, S, Bullock, R, Lillenfield, S, Damaraju, CV.Efficacy of galantamine in probable vascular dementia and Alzheimer’s disease combined with cerebrovascular disease: a randomised trial. Lancet. 2002; 359: 128390.Google Scholar
2.Hassan, A, Hunt, BJ, O’Sullivan, M, et al.Markers of endothelial dysfunction in lacunar infarction and ischaemic leukoaraiosis. Brain. 2003; 126: 42432.Google Scholar
3.Boiten, J, Lodder, J, Kessel, F.Two clinically distinct lacunar infarct entities? A hypothesis. Stroke. 1993; 24: 6526.Google Scholar
4.Tomimoto, H, Akiguchi, I, Wakita, H, Osaki, A, Hayashi, M, Yamamoto, Y.Coagulation activation in patients with Binswanger disease. Arch Neurol. 1999; 56: 11048.Google Scholar
5.Khan, U, Porteous, L, Hassan, A, Markus, H.Risk factor profile of cerebral small vessel disease and its subtypes. J Neurol Neurosurg Psychiatry. 2007; 78: 7026.CrossRefGoogle ScholarPubMed
6.Gouw, AA, Seewann, A, van der Flier, WM, et al.Heterogeneity of small vessel disease: a systematic review of MRI and histopathology correlations. J Neurol Neurosurg Psychiatry. 2011; 82: 12635.CrossRefGoogle ScholarPubMed
7.Di Napoli, M, Papa, F.C-reactive protein and cerebral small-vessel disease an opportunity to reassess small-vessel disease physiopathology? Circulation. 2005; 112: 7815.CrossRefGoogle ScholarPubMed
8.Fornage, M, Chiang, YA, O’Meara, ES, et al.Biomarkers of inflammation and MRI-defined small vessel disease of the brain: the Cardiovascular Health Study. Stroke. 2008; 39: 19529.Google Scholar
9.Annes, JP, Munger, JS, Rifkin, DB.Making sense of latent TGF beta activation. J Cell Sci. 2003; 116: 21724.CrossRefGoogle Scholar
10.Grainger, DJ, Heathcote, K, Chiano, M, et al.Genetic control of the circulating concentration of transforming growth factor type beta1. Hum Mol Genet. 1999; 8: 937.Google Scholar
11.Yokota, M, Ichihara, S, Lin, TL, Nakashima, N, Yamada, Y.Association of a T29->C polymorphism of the transforming growth factor-beta1 gene with genetic susceptibility to myocardial infarction in Japanese. Circulation. 2000; 101: 27837.Google Scholar
12.Investigation committee of guideline for diagnosis and treatment of hyperlipemias, Japan Atherosclerosis Society. Guideline for diagnosis and treatment of hyperlipemias in adults. J Jpn Atheroscler Soc. 1997; 25: 134.CrossRefGoogle Scholar
13.Newton, CR, Graham, A, Heptinstall, LE, et al.Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS). Nucleic Acid Res. 1989; 17: 250316.CrossRefGoogle ScholarPubMed
14.Fazekas, F, Kleinert, R, Offenbacher, H, et al.Pathologic correlates of incidental MRI white matter signal hyperintensities. Neurology. 1993; 43: 16839.CrossRefGoogle ScholarPubMed
15.Sie, MP, Uitterlinden, AG, Bos, MJ, et al.TGF-beta 1 polymorphisms and risk of myocardial infarction and stroke: the Rotterdam Study. Stroke. 2006; 37: 266771.Google Scholar
16.Kim, Y, Lee, C.The gene encoding transforming growth factor beta 1 confers risk of ischemic stroke and vascular dementia. Stroke. 2006; 37: 28435.Google Scholar
17.Herskovits, EH, Itoh, R, Melhem, ER.Accuracy for detection of simulated lesions: comparison of fluid-attenuated inversionrecovery, proton density—weighted, and T2-weighted synthetic brain MR imaging. Am J Roentgenol. 2001; 176: 131318.Google Scholar