Wen Xie

Jining Medical University, Chi-ning-shih, Shandong Sheng, China

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Publications (3)6.81 Total impact

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    ABSTRACT: Mutations in cardiac transcription factor genes, such as GATA-4, NKX2-5 and TBX5 genes, have been associated to the patients with familial and isolated congenital heart disease (CHD). Little work has been done on the epigenetic causes for CHD. Sirtuis are highly conserved NAD-dependent class III deacetylases. In mammals, there are seven members of surtuin family, SIRT1–SIRT7. SIRT1, the closest to yeast Sir2, has deacetylase activity and ADP-ribosyltransferase activity. SIRT1 has been involved in many cellular processes and implicated in human diseases, such as obesity, type 2 diabetes, cancer and neurodegenerative diseases. We hypothesized that altered levels of SIRT1 gene expression, rather than mutations in SIRT1 gene, may contribute to the human diseases. In this study, we genetically analyze the SIRT1 gene promoter in patients with ventricular septal defects (VSD) (n = 333) and ethic-matched healthy controls (n = 348). In all, six single-nucleotide polymorphisms (SNPs) and twelve heterozygous sequence variants were identified. Four novel heterozygous variants, g.69643693A > G, g.69643963A > T, g.69643971G > A and g.69644366Ins, were found in six VSD patients, but in none of controls. Six SNPs and variants, g.69643707A > C (rs35706870), g.69643874C > A, g.69644209C > G, g.69644213G > A, g.69644268T > A and g.69644441G > A, were only identified in controls. The other SNPs and variants were found in both groups with similar frequencies. Therefore, the variants within the SIRT1 gene promoter identified in VSD patients may alter the transcriptional activities of SIRT1 gene promoter. Changed SIRT1 protein levels may contribute to the VSD etiology by affecting the activities of its substrates.
    Biochemical and Biophysical Research Communications 09/2012; 425(4):741–745. · 2.28 Impact Factor
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    ABSTRACT: Congenital heart disease (CHD) is the most common birth defects in humans. The genetic causes for CHD remain largely unknown. T-box transcription factor 1 (TBX1), a dosage-sensitive regulator, plays a critical role in the heart development. Mutations in the coding regions of TBX1 gene have been associated to 22q11 deletion syndrome with cardiac defects and isolated CHD cases, including ventricular septal defect (VSD). To date, TBX1 gene promoter region has not been analyzed and reported in CHD patients. We hypothesized that the sequence variants within TBX1 gene promoter region may change TBX1 levels and mediate CHD development. In this study, the promoter regions of TBX1 gene were genetically and functionally analyzed in 280 VSD patients and 267 healthy controls. Two novel heterozygous variants, g.4353C>T and g.4510A>C, were found in two VSD patients, but in none of controls. The single-nucleotide polymorphism-rs41260844, g.4199T>C, was found more frequent in VSD patients than controls (P < 0.01). Functional analyses revealed that these sequence variants significantly enhanced transcriptional activities of TBX1 gene promoter. Therefore, the sequence variants within TBX1 gene promoter may contribute to the VSD etiology by altering the expression levels of TBX1 gene. Pharmaceutical or genetic manipulation of TBX1 gene expression may provide a novel personalized therapy to prevent and treat late cardiac complications for the adult CHD patients carrying these variants.
    Molecular and Cellular Biochemistry 07/2012; 370(1-2):53-8. · 2.33 Impact Factor
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    ABSTRACT: Congenital heart disease (CHD) is the most common human birth defect. The morbidity and mortality of CHD patients are significantly higher than normal population even after surgical correction of cardiac defects, which is likely caused by genetic defects. To date, genetic causes for CHD remain largely unknown. TBX20 gene encodes a T-box transcription factor that plays pivotal roles in cardiac morphogenesis and is required for maintaining adult heart function and maturation. Mutations in TBX20 gene have been reported in familiar and sporadic CHD patients. However, the promoter region of TBX20 gene has not been genetically analyzed in CHD patients. As TBX20 functions as a dosage-dependent regulator during the heart development, we hypothesized that the sequence variants within the promoter region of the TBX20 gene may contribute to CHD. In this study, we bi-directionally sequenced the promoter region of the TBX20 gene in 265 patients with ventricular septal defects (VSD) and 242 controls. Within the promoter region of the TBX20 gene, one single-nucleotide polymorphism (SNP), rs336284 (g.4740T>C), and one novel heterozygous variant g.4741 G>A, which was linked with rs336284 (g.4740 T>C), were found in both VSD patients and controls with similar frequencies. A novel heterozygous variant, g.4932 G>A, was found in one VSD patient, but in none of controls, which significantly inhibited the transcriptional activities of TBX20 gene promoter, suggesting that the variant may contribute to the VSD etiology. Therefore, our data provides new information with respect to TBX20 gene mutations in CHD patients.
    Gene 03/2012; 500(1):28-31. · 2.20 Impact Factor