[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Chronic obstructive pulmonary disease (COPD) is influenced by both environmental and genetic factors. Few gene studies of the Chinese population have focused on COPD. We investigated candidate genes associated with susceptibility to COPD in the Chinese Han population. METHODS: A total of 331 COPD patients and 213 control subjects were recruited for this study. Nighty-seven single-nucleotide polymorphisms (SNPs) of 46 genes were selected for genotyping. Genotypes were determined using multiplex polymerase chain reaction (PCR). RESULTS: Significant differences between patients and healthy controls were observed in the allele frequencies of seven SNPs: rs1205 C, rs2353397 C, rs20541 T, rs2070600 G, rs10947233 G, rs1800629 G, and rs2241712 A. After Bonferroni correction, rs2353397 C was most strongly associated with susceptibility to COPD. Haplotype analysis showed that the frequencies of the GC, GT haplotypes of rs2241718 (TGF-beta1 gene), and rs6957 (CDC97 gene) were significantly higher in the control group than in the COPD case group (p=1.88x10-9); the frequencies of the TT haplotype of rs1205 and rs2808630 (CRP gene) were significantly higher in the control group (p=0.0377). CONCLUSION: Our study suggests some genetic variants associated with the susceptibility of COPD in the Chinese Han population.
BMC Medical Genomics 12/2012; 5(1):64. · 3.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Systemic corticosteroids (SCS) have been shown to improve the outcome of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, the optimal dose remains controversial. OBJECTIVES: We performed a meta-analysis to evaluate whether high-dose SCS is better. METHODS: We searched PubMed, EMBASE, CPCI-S and CENTRAL databases and references of reviews or meta-analyses to identify randomized controlled trials using SCS in AECOPD. We performed a routine meta-analysis to evaluate the effects of SCS on treatment failure rate and FEV1 improvement compared with placebo in AECOPD. Subgroup analysis was performed by dividing the studies into a high-dose group (initial dose >=80 mg PE/d) and a low-dose group (initial dose 30-80 mg PE/d) in all patients and in only inpatients. Meta-regression was performed using initial dose as an independent factor. We classified the suspected adverse effects into several groups and combined them separately. RESULTS: Our search yielded 12 studies involving 1172 patients. SCS use was associated with a significant reduction in the treatment failure rate (RR 0.58; 95%CI: 0.46 to 0.73) and improvement in ΔFEV1 (0.11L; 95%CI: 0.08 to 0.14L). The high-dose regimen did not show superiority to the low-dose regimen. No obvious correlation was found between the SCS effect and the initial dose. SCS led to an obvious increase in hyperglycemia risk. However, the high-dose group did not show obviously higher risk of adverse effects. CONCLUSION: SCS can reduce treatment failure rate and improve lung function in AECOPD. The low-dose regimen (initial dose 30-80mg/d PE) is proper for treating AECOPD.
The Clinical Respiratory Journal 10/2012; · 1.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The risk of developing chronic obstructive pulmonary disease (COPD) is partially determined by genetic and environmental factors. Many published candidate gene studies show conflicting results due to ethnic differences and sample sizes. The number of these studies carried out in Chinese populations is small. To investigate candidate genes and haplotypes for susceptibility to COPD in a southern Han Chinese population, we performed genotyping of DNA samples in 200 COPD patients and 250 control subjects by analyzing 54 single-nucleotide polymorphisms (SNPs) in 23 genes associated with the development of COPD and/or pulmonary function identified by genome-wide association studies (GWAS). We also performed linkage disequilibrium (LD) and haplotype analysis according to the results of genotyping. The frequencies of the SNP [rs3749893 of testis‑specific protein Y-encoded-like 4 (TSPYL-4) gene] G allele and SNP [rs1052443 of 5'-nucleotidase domain containing 1 (NT5DC1) gene] A allele were significantly higher in the cases studied compared to the control subjects (P=0.032, P<0.05, OR=0.692, 95% CI 0.495‑0.970; P=0.0205, P<0.05, OR=0.670, 95% CI 0.477-0.941, respectively). Results showed that two blocks of SNPs (rs1052443 and rs3749893; rs11155242 and rs6937121) had sufficient precision to allow construction of a haplotype block. We constructed the TSPYL-4 and NT5DC1 haplotypes of the cases and controls, but no significant difference between the two groups was found. rs3749893 A allele of TSPYL-4 and rs1052443 C allele of NT5DC1 were associated with a protective effect against the deterioration of pulmonary function. In conclusion, TSPYL-4 and NT5DC1 gene polymorphisms are associated with susceptibility to COPD and pulmonary function.
Molecular Medicine Reports 06/2012; 6(3):631-8. · 1.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patients with chronic obstructive pulmonary disease (COPD) respond poorly to corticosteroids. Histone deacetylase-2 (HDAC-2) plays a pivotal role in many cases of steroid insensitivity. The main aim of this study was to restore the smoking-induced reduction in corticosteroid sensitivity by increasing HDAC-2 activity using low-dose theophylline. Rats were exposed to cigarette smoke (CS) and treated with budesonide and two doses of theophylline. Besides the pathologic examination and cell counting in the bronchoalveolar lavage fluid (BALF), the expression of HDAC-2 and CXC chemokine ligand-8 (CXCL-8) were measured. Airway inflammation induced by CS was demonstrated by pathologic changes of lung tissue and increased level of CXCL-8. CS exposure also markedly decreased HDAC-2 expression. Moreover, a negative correlation was found between HDAC-2 activity and a lung destruction index. The index was restored to control levels with inhaled corticosteroid treatment in combination with a low, not a high, dose of theophylline. These results indicate that low-dose theophylline might provide protection from smoke damage and improve the anti-inflammatory effects of steroids by increasing HDAC-2 activity.
Canadian Journal of Physiology and Pharmacology 06/2012; 90(7):895-902. · 1.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abnormalities in the transforming growth factor-β(1) (TGF-β(1)) gene are thought to be linked to chronic obstructive pulmonary disease (COPD). We investigated the association between the single nuclear polymorphisms (SNPs) of TGF-β(1) and the risk of COPD in a case-control study and meta-analysis. We genotyped 160 cases and 177 control subjects in a local hospital using the Mass-Array(TM) Technology Platform and then tested the association of four SNPs in TGF-β(1) (rs6957, rs1800469, rs2241712, and rs2241718) with COPD. Plasma TGF-β(1) level measurement was performed later. A database covering all papers published up to October 30, 2010, was then reviewed. Statistical analysis was performed using Revman 5.0 and STATA 11.0 software. No association was found between TGF-β(1) gene SNPs and an increased risk of COPD in Asians. By meta-analysis, the link of two polymorphisms, rs1800469 and rs1982073, was investigated in seven and eight studies, respectively, involving 1,508 COPD patients and 2,608 control subjects. The results showed that there was no significant association between an increased risk of COPD in carriers of the T allele (TT+TC) versus the CC genotype in rs1800469 and rs1982073. In ethnic subgroup analysis, the risk of COPD associated with the rs1800469 T allele was not significantly elevated among Asians. TGF-β(1) gene polymorphisms are not associated with an increased risk of COPD in the Asian population.
Beiträge zur Klinik der Tuberkulose 06/2011; 189(3):213-23. · 2.06 Impact Factor