Correlation between gene polymorphisms of CYP1A1, GSTP1, ERCC2, XRCC1, and XRCC3 and susceptibility to lung cancer.

Lung cancer is a common malignant tumor that is characterized by high morbidity and poor prognosis. Studies suggest that an individual's genetic background affects the risk of developing lung cancer. Therefore, we investigated the relationship between gene polymorphisms and susceptibility to lung cancer. We recruited 308 primary lung cancer patients as subjects and 253 healthy adults as controls. After extraction of DNA from blood samples, gene polymorphisms in CYP1A1, GSTP1, ERCC2, XRCC1, and XRCC3 were investigated by polymerase chain reaction and restriction fragment length polymorphism. The frequencies of the genotypes in both groups were investigated to obtain odds ratios and 95% confidence intervals, and correlation analysis was carried out. The analysis results showed that the following polymorphisms were correlated with susceptibility to lung cancer: rs4646903 in CYP1A1 (P < 0.001), rs1048943 in CYP1A1 (P < 0.001), rs1695 in GSTP1 (P < 0.05), rs13181 in ERCC2 (P < 0.001), and rs25487 in XRCC1 (P < 0.05); no such correlation existed in rs861539 in XRCC3 (P > 0.05). The study revealed that the more high-risk gene polymorphisms a patient carries, the greater the risk of developing lung cancer. Carriers of rs4646903 in CYP1A1, rs1048943 in CYP1A1, rs1695 in GSTP1, rs13181 in ERCC2, and rs25487 in XRCC1 are more likely to develop lung cancer.

Association between the Val34Leu polymorphism in blood coagulation factor XIII-A and intracerebral hemorrhage: a meta-analysis.

Although the Val34Leu polymorphism in blood coagulation factor XIII-A (FXIII-A) has been implicated in the pathogenesis of intracerebral hemorrhage (ICH), the results of research conducted thus far have been inconclusive. In this meta-analysis, we have assessed the association between the FXIII-A Val34Leu polymorphism and ICH risk. Published reports pertaining to this association were retrieved from the PubMed database, and the data from these studies were pooled and statistically analyzed with Stata 12.0. Summary odds ratios (OR) and 95% confidence intervals (95%CI) were calculated according to a fixed-effect or a random-effect model (as appropriate). The initial search identified 520 articles, only seven of which (retrospective studies) met the inclusion criteria and were included in this meta-analysis. These studies comprised 727 ICH patients and 1968 controls. The results of a combined analysis showed no significant association between the FXIII-A Val34Leu polymorphism and ICH risk in the overall population (Leu/Leu vs Val/Val: OR = 1.41, 95%CI = 0.82-2.43; Val/Leu vs Val/Val: OR = 1.08, 95%CI = 0.89-1.30; dominant model: OR = 1.14, 95%CI = 0.95-1.36; recessive model: OR = 0.72, 95%CI = 0.43-1.22). The results of this meta-analysis suggest that the FXIII-A Val34Leu polymorphism is not associated with ICH risk in a Caucasian population. Further large and well-designed studies must be conducted to confirm this preliminary conclusion.

Characterization of MUSTN1 gene and its relationship with skeletal muscle development at postnatal stages in Pekin ducks.

Musculoskeletal embryonic nuclear protein 1 (MUSTN1) gene is involved in myogenic fusion and differentiation in rats. We previously showed the differential expression of MUSTN1 in week (W) 2 and W6 breast muscles of Pekin ducks. In this study, we further investigated its molecular characteristics and expression profiles in different tissues at W7 and in breast and leg muscles at W1, W3, W5, W7, and W9. The relationship between muscle development and muscle fiber areas was also investigated. A 358-bp cDNA sequence was obtained. The coding sequence of duck MUSTN1 cDNA encoded a 78-amino acid sequence, which showed high similarity with those of other species (96% similarity with zebra finch and 94% with chicken). In addition, a 6435-bp genomic DNA sequence of MUSTN1 was obtained. In total, 231 transcription factor-binding sites were found in the promoter region, and many of these transcription factors were involved in the regulation of muscle development. MUSTN1 expression in breast muscle increased from W1 to W5 and then decreased at W9. In leg muscle, the expression increased from W1 to W3 and then decreased. The relative growth rates of breast and leg muscle fibers reached their peaks at W3-W5 and W1-W3, respectively. Since the greatest relative growth rates appeared at the highest expression levels of the MUSTN1 gene, it was thought to play roles in duck muscle development. Our findings would be helpful in understanding the molecular characteristics and functions of the MUSTN1 gene in breast muscle development of ducks.

Gene expression profile and enrichment pathways in different stages of bladder cancer.

Bladder cancer is a highly heterogeneous neoplasm. We examined the gene expression profile in 3 bladder cancer stages (Ta, T1, T2) using expression microarray analysis of 40 bladder tumors. Differentially expressed genes were found by the t-test, with <0.005 as the significance threshold. KEGG pathway-enrichment analysis was used to study the signaling pathways of the genes. We found 36 genes that could be used as molecular markers for predicting the transition from Ta-T1 to T1-T2. Among these, 11 overlapped between Ta-T1 and T1-T2 stages. Six genes were down-regulated at the Ta-T1 stage, but were up-regulated at the T1-T2 stage (ANXA5, ATP6V1B2, CTGF, GEM, IL13RA1, and LCP1); 5 genes were up-regulated at the Ta-T1 stage, but down-regulated at the T1-T2 stage (ACPP, GNL1, RIPK1, RAPGEF3, and ZER1). Another 25 genes changed relative expression levels at the T1-T2 stage. These genes (including COL1A1, COL1A2, FN1, ITGA5, LGALS1, SPP1, VIM, POSTN, and COL18A1) may be involved in bladder cancer progression by affecting extracellular matrix-receptor interaction and focal adhesion. The cytokine-cytokine receptor interaction, neuroactive ligand-receptor interaction, and calcium-signaling pathway were associated with bladder cancer progression at both the Ta-T1 and T1-T2 stages.

Characterization of myostatin gene (MSTN) of Pekin duck and the association of its polymorphism with breast muscle traits.

Myostatin, encoded by the MSTN gene, is a negative regulator of muscle growth, and its expression level in muscle tissue is closely correlated with muscle growth and satellite cell proliferation. To identify the characteristics of the Pekin duck MSTN gene and the relationship between its polymorphism and breast muscle traits in Pekin duck, cDNA cloning and analysis and the expression pattern in breast muscle development and polymorphism were performed using molecular cloning, quantitative real-time reverse-transcription polymerase chain reaction, and molecular marker technology. The results showed that a 1320-bp sequence, including a 93-bp 5'-UTR, 1128-bp CDS, and 99- bp 3'-UTR, was obtained, and two alternative splicing isoforms were detected. The alternative splicing isoforms encoded 375- and 251-amino acid residues. The amino acid sequence of Pekin duck MSTN was similar to other vertebrates and exhibited the highest similarity to chicken. The expression pattern of MSTN in breast muscle tissue showed a tendency to increase, except for a slight decrease at 6 weeks. Three single nucleotide polymorphisms were found in the Pekin duck MSTN gene by cDNA sequencing from different individuals. The T129C had significant association with breast muscle thickness, and the T952C had significant association with the fossilia ossis mastodi length. This study reveals the molecular characteristics of the Pekin duck MSTN gene and the relationship of its polymorphism with breast muscle traits in Pekin duck. Therefore, it can provide some useful basic understanding of MSTN functions.

Small molecule-enrichment analysis in response to osmotic stimuli in the intervertebral disc.

The intervertebral disc (IVD) is a heterogeneous structure that contributes to load support and flexibility in the spine. IVD cells experience a broad range of physical stimuli under physiological conditions, including alterations in their osmotic environment. To date, the molecular mechanisms regulating the response of IVD to osmotic pressure are still not well understood. We obtained the gene expression profile of human IVD cells from NCBI and looked for potential therapeutic drug candidates. Based on microarray data, we concluded that RAP2A and GNA13 appear to have a role in response to osmotic stimuli in intervertebral discs. Using a computational bioinformatics method, we determined that thioridazine has potential as a therapeutic drug candidate for regulating osmotic pressure changes in IVD cells. We anticipate that our results will be used to generate hypotheses for laboratory, patient, and population-based studies.