AIM: Considerable attention is focused on polymorphisms in the gene encoding transforming growth factor-pi (TGF-β1), a multifunctional cytokine that is in turn a potent growth inhibitor involved in wound healing and ...AIM: Considerable attention is focused on polymorphisms in the gene encoding transforming growth factor-pi (TGF-β1), a multifunctional cytokine that is in turn a potent growth inhibitor involved in wound healing and differentiation. In humans, it promotes the pathogenesis of organ fibrosis, atherosclerosis, cancer, autoimmune and inflammatory diseases, keloid disease, and hypertrophic scarring. For this reason, much emphasis has been placed on studies elucidating the impact of TGF-β1 and its gene variations for the susceptibility and pathogenesis of these diseases. Unfortunately, some studies have serious limitations. METHODS: We have recently described a high-throughput method for investigation the Arg25Pro polymorphism of human TGF-β1 gene and showed that the frequency of the Pro25 allele is significantly associated with hepatic fibrogenesis. In this report, we describe two novel LightCyder (LC) techniques that facilitate the examination of the two other known alterations in the coding region of TGF-β1. We investigated whether these polymorphisms contribute to hepatitis-induced progression of fibrogenesis in Chinese and Caucasians. RESULTS: In the Chinese ancestry, the gene polymorphisms at codons 25 and 263 were not found and the genetic variant at codon 10 is unlikely to confer susceptibility to hepatic fibrosis. Contrarily, in Caucasians TGF-β1 allelic variations are more frequent and the presence of prolines either in codon 25 or 10 is associated with the interindividual variability in developing more severe fibrosis during chronic hepatitis C infection. CONCLUSION: In summary, these results confirm the hypothesis that TGF-β1 polymorphisms are associated with fibrosis progression in Caucasians chronically infected with hepatitis C.展开更多
AIM： To identify molecular markers shared across South African esophageal squamous cell carcinoma （ESCC） cell lines using o/togenetics, fluorescence in situ hybridization （FISH） and single nucleotide polymorphism...AIM： To identify molecular markers shared across South African esophageal squamous cell carcinoma （ESCC） cell lines using o/togenetics, fluorescence in situ hybridization （FISH） and single nucleotide polymorphism （SNP） array copy number analysis. METHODS： We used conventional cytogenetics, FISH, and multicolor FISH to characterize the chromosomal rearrangements of five ESCC cell lines established in South Africa. The whole genome copy number profile was established from 250K SNP arrays, and data was analyzed with the CNAT 4.0 and GISTIC software. tions involved the following chromosomal regions and genes： 11q13.3 （CCND1, FGF3, FGF4, FGF19, MYEOV）, 8q24.21（C-MYC, FAM84B）, 11q22.1-q22.3 （B[RC2, BIRC3）, 5p15.2 （CTNND2）, 3qll.2-q12.2 （MINA） and 18p11.32 （TYMS, YES1）. The significant deletions included 1p31.2-p31.1 （CTH, GADD45a, DIRAS3）, 2q22.1 （LRPIB）, 3p12.1-p14.2 （FHIT）, 4q22.1-q32.1 （CASP6, SMAD1）, 8p23.2-q11.1 （BNIP3L） and 18q21.1-q21.2 （SMAD4, DCC）. The 3p11.2 translocation breakpoint was shared across four cell lines, supporting a role for genes involved at this site, in particular, the EPHA3 gene which has previously been reported to be deleted in ESCC.CONCLUSION： The finding that a significant number of genes that were amplified （FGF3, FGF4, FGF19, CCND1 and C-MYC） or deleted （SFRP2 gene） are involved in the Wnt and fibroblast growth factor signaling pathways, suggests that these pathways may be activated in these cell lines.展开更多
Myostatin （MSTN） is a member of the transforming growth factor-β gene superfamily that negatively regulates skeletal muscle development and growth. In the present study, partial genomic fragments of Myostatin-1 （M...Myostatin （MSTN） is a member of the transforming growth factor-β gene superfamily that negatively regulates skeletal muscle development and growth. In the present study, partial genomic fragments of Myostatin-1 （MSTN-1） in two commercial hatchery populations of Ancherythroculter nigrocauda, an economically important freshwater fish, were screened for single nucleotide polymorphisms （SNPs） and then genotyped by direct sequencing of PCR products. Five SNPs were identified in intron 1 and exon 2, including a non-synonymous mutation causing an amino acid change （Val to Ile） at position 180. Association analyses based on 300 individuals revealed that the g. 1129T〉C SNP locus was significantly associated with total length （TL）, body length （BL）, body height （BH） and body weight （BW） in 6- and 18-month-old populations, while the g. 1289G〉A locus was significantly associated with BH and BW in the 6-month-old population. Haplotype analyses revealed that fish with the genotype combinations TC/TC or TC/GA showed better growth performance. Our results suggest that g.l129T〉C and g.1289G〉A have positive effects on growth traits and may be candidate gene markers for marker-assisted selection in A. nigrocauda.展开更多
Objective:We investigated the potential association between vascular endothelial growth factor(VEGF) polymorphisms and the risk of lung cancer.Methods:In the case-control study, we used PCR-RFLP technique to determine...Objective:We investigated the potential association between vascular endothelial growth factor(VEGF) polymorphisms and the risk of lung cancer.Methods:In the case-control study, we used PCR-RFLP technique to determine two VEGF genotypes-2578C/A and 936C/T in 171 lung cancer patients and 172 healthy controls for conformation, and constructed haplotypes of the two gene sites by PHASE1.0 software.Unconditional logistic regression model was used to analyze the statistical association of genontypes or haplotypes in the two groups adjusted by gender and age.Results:Compared with at least one-2578A allele, individuals with-2578CC genotype found associated with a significantly decreased risk of lung cancer P=0.001;adjusted odds ratio(OR), 0.391;95% confidence interval(95% CI), 0.226-0.686.Analyses stratified by gender showed that the combined-2578 CA and AA genotype were also associated with a significantly decreased risk of lung cancer.(P = 0.016;OR = 0.303;95% CI = 0.153-0.601 and P = 0.018;OR = 0.547;95% CI = 0.331-0.903, respectively).The distribution of the two haplotypes(936C/-2578C and 936C/-2578A) were significantly different between case-and-control groups(P = 0.016, OR = 0.317, 95% CI = 0.124-0.809 and P = 0.018, OR = 0.547, 95% CI = 0.331-0.903).Analyses categorized by tumor histology showed that Haplotype C-C was associated with a significantly decreased risk of adenocarcinoma compared with the reference haplotypes.(P = 0.004;OR = 0.237;95% CI = 0.090-0.627).Conclusion:These results suggest that the VEGF polymorphisms may be a critical factor for the risk of lung cancer.展开更多
基金Supported by the Grants From the Federal Ministry of Education and Research of Germany (Network of Competence in Medicine HepNet)the Natural Science Foundation of China, No. 30270605
文摘AIM: Considerable attention is focused on polymorphisms in the gene encoding transforming growth factor-pi (TGF-β1), a multifunctional cytokine that is in turn a potent growth inhibitor involved in wound healing and differentiation. In humans, it promotes the pathogenesis of organ fibrosis, atherosclerosis, cancer, autoimmune and inflammatory diseases, keloid disease, and hypertrophic scarring. For this reason, much emphasis has been placed on studies elucidating the impact of TGF-β1 and its gene variations for the susceptibility and pathogenesis of these diseases. Unfortunately, some studies have serious limitations. METHODS: We have recently described a high-throughput method for investigation the Arg25Pro polymorphism of human TGF-β1 gene and showed that the frequency of the Pro25 allele is significantly associated with hepatic fibrogenesis. In this report, we describe two novel LightCyder (LC) techniques that facilitate the examination of the two other known alterations in the coding region of TGF-β1. We investigated whether these polymorphisms contribute to hepatitis-induced progression of fibrogenesis in Chinese and Caucasians. RESULTS: In the Chinese ancestry, the gene polymorphisms at codons 25 and 263 were not found and the genetic variant at codon 10 is unlikely to confer susceptibility to hepatic fibrosis. Contrarily, in Caucasians TGF-β1 allelic variations are more frequent and the presence of prolines either in codon 25 or 10 is associated with the interindividual variability in developing more severe fibrosis during chronic hepatitis C infection. CONCLUSION: In summary, these results confirm the hypothesis that TGF-β1 polymorphisms are associated with fibrosis progression in Caucasians chronically infected with hepatitis C.
文摘AIM： To identify molecular markers shared across South African esophageal squamous cell carcinoma （ESCC） cell lines using o/togenetics, fluorescence in situ hybridization （FISH） and single nucleotide polymorphism （SNP） array copy number analysis. METHODS： We used conventional cytogenetics, FISH, and multicolor FISH to characterize the chromosomal rearrangements of five ESCC cell lines established in South Africa. The whole genome copy number profile was established from 250K SNP arrays, and data was analyzed with the CNAT 4.0 and GISTIC software. tions involved the following chromosomal regions and genes： 11q13.3 （CCND1, FGF3, FGF4, FGF19, MYEOV）, 8q24.21（C-MYC, FAM84B）, 11q22.1-q22.3 （B[RC2, BIRC3）, 5p15.2 （CTNND2）, 3qll.2-q12.2 （MINA） and 18p11.32 （TYMS, YES1）. The significant deletions included 1p31.2-p31.1 （CTH, GADD45a, DIRAS3）, 2q22.1 （LRPIB）, 3p12.1-p14.2 （FHIT）, 4q22.1-q32.1 （CASP6, SMAD1）, 8p23.2-q11.1 （BNIP3L） and 18q21.1-q21.2 （SMAD4, DCC）. The 3p11.2 translocation breakpoint was shared across four cell lines, supporting a role for genes involved at this site, in particular, the EPHA3 gene which has previously been reported to be deleted in ESCC.CONCLUSION： The finding that a significant number of genes that were amplified （FGF3, FGF4, FGF19, CCND1 and C-MYC） or deleted （SFRP2 gene） are involved in the Wnt and fibroblast growth factor signaling pathways, suggests that these pathways may be activated in these cell lines.
基金Supported by the National Science Foundation for Young Scientists of China(No.31402296)the National Science Foundation for Post-Doctoral Scientists of China(No.2014M562077)the Wuhan Chenguang Project for Young Scholars(No.201372304010832)
文摘Myostatin （MSTN） is a member of the transforming growth factor-β gene superfamily that negatively regulates skeletal muscle development and growth. In the present study, partial genomic fragments of Myostatin-1 （MSTN-1） in two commercial hatchery populations of Ancherythroculter nigrocauda, an economically important freshwater fish, were screened for single nucleotide polymorphisms （SNPs） and then genotyped by direct sequencing of PCR products. Five SNPs were identified in intron 1 and exon 2, including a non-synonymous mutation causing an amino acid change （Val to Ile） at position 180. Association analyses based on 300 individuals revealed that the g. 1129T〉C SNP locus was significantly associated with total length （TL）, body length （BL）, body height （BH） and body weight （BW） in 6- and 18-month-old populations, while the g. 1289G〉A locus was significantly associated with BH and BW in the 6-month-old population. Haplotype analyses revealed that fish with the genotype combinations TC/TC or TC/GA showed better growth performance. Our results suggest that g.l129T〉C and g.1289G〉A have positive effects on growth traits and may be candidate gene markers for marker-assisted selection in A. nigrocauda.
基金Supported by a grant from the Shandong Provincal Natural SciencesFoundation (No. 2005ZX04).
文摘Objective:We investigated the potential association between vascular endothelial growth factor(VEGF) polymorphisms and the risk of lung cancer.Methods:In the case-control study, we used PCR-RFLP technique to determine two VEGF genotypes-2578C/A and 936C/T in 171 lung cancer patients and 172 healthy controls for conformation, and constructed haplotypes of the two gene sites by PHASE1.0 software.Unconditional logistic regression model was used to analyze the statistical association of genontypes or haplotypes in the two groups adjusted by gender and age.Results:Compared with at least one-2578A allele, individuals with-2578CC genotype found associated with a significantly decreased risk of lung cancer P=0.001;adjusted odds ratio(OR), 0.391;95% confidence interval(95% CI), 0.226-0.686.Analyses stratified by gender showed that the combined-2578 CA and AA genotype were also associated with a significantly decreased risk of lung cancer.(P = 0.016;OR = 0.303;95% CI = 0.153-0.601 and P = 0.018;OR = 0.547;95% CI = 0.331-0.903, respectively).The distribution of the two haplotypes(936C/-2578C and 936C/-2578A) were significantly different between case-and-control groups(P = 0.016, OR = 0.317, 95% CI = 0.124-0.809 and P = 0.018, OR = 0.547, 95% CI = 0.331-0.903).Analyses categorized by tumor histology showed that Haplotype C-C was associated with a significantly decreased risk of adenocarcinoma compared with the reference haplotypes.(P = 0.004;OR = 0.237;95% CI = 0.090-0.627).Conclusion:These results suggest that the VEGF polymorphisms may be a critical factor for the risk of lung cancer.
