DNA sequencing of TGFβ2 in sporadic patients with tetralogy of Fallot
- Authors:
- Yan Gao
- Xiao-Jing Ma
- Guo-Ying Huang
- Jing Zhang
- Hui-Jun Wang
- Duan Ma
- Yao Wu
View Affiliations
Affiliations: Cardiac Center, Children's Hospital of Fudan University, Shanghai 201102, P.R. China, Institute of Biomedical Sciences, Fudan University, Shanghai 200032, P.R. China
- Published online on: February 21, 2012 https://doi.org/10.3892/etm.2012.492
-
Pages:
878-880
Metrics: Total
Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
This article is mentioned in:
Abstract
Transforming growth factor β2 (TGFβ2) plays an essential role in cardiac morphogenesis. However, the prevalence of TGFβ2 mutations in congenital heart disease (CHD) and the correlation between the TGFβ2 genotype and the CHD phenotype have not been studied extensively. The aim of this study was to examine DNA sequence changes in the TGFβ2 gene in sporadic patients with tetralogy of Fallot (TOF), and to observe whether TGFβ2 is the susceptibility gene for TOF. A cohort of 100 pediatric patients with TOF was recruited to the study; 200 healthy children were used as controls. PCR and genotyping were conducted for the detection of DNA changes in TGFβ2. The exons and the 5' untranslated region (5'UTR) sequences of the TGFβ2 gene were amplified. No mutations were identified in the coding region in any of the TOF patients. However, three single nucleotide changes, including 9126 A>AC, 9353 A>AG and 9040_9043 del CTTC, in the 5'UTR were found. There were no significant differences in allelic frequencies and genotype frequencies of position 9126 and 9353 between the TOF group and the control group. On the contrary, a significant difference was identified in the allelic frequencies (χ2=17.469, P<0.001) of position 9040_9043 in the 5'UTR between the TOF group and the control group. Our results suggest that TGFβ2 may be a potential candidate gene of TOF. SNPs at position 9040_9043 del CTTC in the 5'UTR of TGFβ2 may be associated with susceptibility to TOF. The CTTC allele may be the susceptibility allele for TOF. However, the exact effect of these sequence changes requires further study using functional experiments.
View References
|
1.
|
Nemer M: Genetic insights into normal and
abnormal heart development. Cardiovasc Pathol. 17:48–54. 2008.
View Article : Google Scholar : PubMed/NCBI
|
|
2.
|
Srivastava D and Olson EN: A genetic
blueprint for cardiac development. Nature. 407:221–226. 2000.
View Article : Google Scholar : PubMed/NCBI
|
|
3.
|
Loffredo CA, Silbergeld EK, Ferencz C, et
al: Association of transposition of the great ateries in infants
with maternal exposures to herbicides and rodenticides. Am J
Epidemiol. 153:529–536. 2001. View Article : Google Scholar : PubMed/NCBI
|
|
4.
|
Dunker N and Krieglstein K: Targeted
mutations of transforming growth factor-beta genes reveal important
roles in mouse development and adult homeostasis. Eur J Biochem.
267:6982–6988. 2000. View Article : Google Scholar : PubMed/NCBI
|
|
5.
|
Feng XH and Derynck R: Specificity and
versatility in TGF-β signaling through Smads. Cell Dev Biol.
21:659–693. 2005.PubMed/NCBI
|
|
6.
|
Barton DE, Foellmer BE, Du J, et al:
Chromosomal mapping of genes for transforming growth factors beta-2
and beta-3 in man and mouse: dispersion of TGF-beta gene family.
Oncogene Res. 3:323–331. 1988.PubMed/NCBI
|
|
7.
|
Sanford LP, Ormsby I, Gittenberger-de
Groot AC, et al: TGFβ2 knockout mice have multiple developmental
defects that are non-overlapping with other TGFβ knockout
phenotypes. Development. 124:2659–2670. 1997.
|
|
8.
|
Proetzel G, Pawlowski SA, Wiles MV, et al:
Transforming growth factor-beta 3 is required for secondary palate
fusion. Nat Genet. 11:409–414. 1995. View Article : Google Scholar : PubMed/NCBI
|
|
9.
|
Shull MM, Ormsby I, Kier AB, et al:
Targeted disruption of the mouse transforming growth factor-beta 1
gene results in multifocal inflammatory disease. Nature.
359:693–699. 1992. View
Article : Google Scholar : PubMed/NCBI
|
|
10.
|
Bartram U, Molin DG, Wisse LJ, et al:
Double-outlet right ventricle and overriding tricuspid valve
reflect disturbances of looping, myocardialization, endocardial
cushion differentiation, and apoptosis in TGF-beta(2)-knockout
mice. Circulation. 103:2745–2752. 2001. View Article : Google Scholar
|
|
11.
|
Azhar M, Schultz JEJ, Grupp I, et al:
Transforming growth factor beta in cardiovascular development and
function. Cytokine Growth Factor Rev. 14:391–407. 2003. View Article : Google Scholar : PubMed/NCBI
|
|
12.
|
Kubalak SW, Hutson DR, Scott KK, et al:
Elevated transforming growth factor beta2 enhances apoptosis and
contributes to abnormal outflow tract and aortic sac development in
retinoic X receptor alpha knockout embryos. Development.
129:733–746. 2002.
|
|
13.
|
Hughes TA: Regulation of gene expression
by alternative untranslated regions. Trends Genet. 22:119–122.
2006. View Article : Google Scholar : PubMed/NCBI
|
|
14.
|
Gray NK and Wickens M: Control of
translation initiation in animals. Annu Rev Cell Dev Biol.
14:399–458. 1998. View Article : Google Scholar : PubMed/NCBI
|
|
15.
|
Mignone F, Gissi C, Liuni S, et al:
Untranslated regions of mRNAs. Genome Biol 3: REVIEWS0004. 2002.
View Article : Google Scholar
|
