AIM: Clinical and experimental data suggest that gut-derived endotoxins are an important pathogenic factors for progression of chronic liver disease. Recently, a C-T (-159)polymorphism in the promoter region of the CD...AIM: Clinical and experimental data suggest that gut-derived endotoxins are an important pathogenic factors for progression of chronic liver disease. Recently, a C-T (-159)polymorphism in the promoter region of the CD14 gene was detected and found to confer increased CD14 expression and to be associated with advanced alcoholic liver damage. Here, we investigated this polymorphism in patients with less advanced alcoholic liver disease (ALD)and chronic hepatitis C virus (HCV) infection.METHODS: CD14 genotyping was performed by PCR-RFLP analysis in (a) 121 HCV patients, (b) 62 patients with alcohol-associated cirrhosis (Alc-Ci), (c) 118 individuals with heavy alcohol abuse without evidence of advanced liver damage (Alc-w/o Ci), and (d) 247 healthy controls.Furthermore, serum levels of soluble CD14 (sCD14) and transaminases were determined.RESULTS: The TT genotype was significantly more frequent in Alc-Ci compared to Alc-w/o Ci or controls (40.3% vs 23.7% or 24.0%, respectively). In Alc-w/o Ci,serum levels of transaminases did not differ significantly between patients with different CD14 genotypes. In HCV patients, TT-homozygotes had significantly higher sCD14 levels and sCD14 serum levels were significantly higher in patients with advanced fibrosis or cirrhosis. However,no association was found between CD14 genotypes and histological staging or grading.CONCLUSION: Considering serum transaminases as surrogate markers for alcoholic liver damage, the CD14 polymorphism seems to exhibit different effects during the course of ALD. Differences in genotype distribution between cirrhotic HCV patients and alcoholics and the known functional impact of this polymorphism on CD14 expression levels further indicate differences in the pathophysiological role of CD14 and CD14-mediated lipopolysaccharides signal transduction with regard to the stage as well as the type of the underlying liver disease.展开更多
AIM: To investigate whether single-nucleotide polymor- phisms in the promoter regions of endotoxin-responsive genes CD14 C (-159) T is associated with chronic hepatitis B. METHODS: We obtained genomic DNA from 80 pati...AIM: To investigate whether single-nucleotide polymor- phisms in the promoter regions of endotoxin-responsive genes CD14 C (-159) T is associated with chronic hepatitis B. METHODS: We obtained genomic DNA from 80 patients with established diagnosis of chronic hepatitis B and 126 healthy subjects served as a control population. The CD 14 C (-159) T polymorphism was investigated using an allele specific PCR method. RESULTS: Twenty seven percent of chronic hepatitis B patients and 75% of controls were heterozygous for CT genotype. The difference between the chronic hepatitis B and control groups was statistically significant [P < 0.0001; Odds ratio (OR) = 2.887; 95% CI: 1.609-5.178]. Twenty four point six percent of chronic hepatitis B and patients 12.3% of the control group were heterozygous for TT genotype. The difference between groups was not statistically significant (P = 0.256; OR = 0.658; 95% CI: 0.319-1.358). Forty eight point four percent of chronic hepatitis B patients and 12.7% of control were homozy- gote for CC genotype (P < 0.004; OR = 0.416; 95% CI: 0.229-0.755). The frequency of allele C was 61.9% and allele T was 38.1% in hepatitis B patients group. The frequency of allele C was 55.2% and allele T was 44.8% for the control group (P = 0.179; OR = 1.319; 95% CI: 0.881-1.977). CONCLUSION: The TT heterozygous genotype was not a risk factor for chronic hepatitis B. CC homozygote genotype is protective for hepatitis B. Lack of heterozy- gosis of genotype CT is a risk factor for chronic hepatitis B. Alleles C or T were not risk factors for chronic hepatitis B. These findings show the role of a single-nucleotide polymorphism at CD14/-159 on the development ofchronic hepatitis B. Endotoxin susceptibility may play a role in the pathogenesis of chronic hepatitis B.展开更多
目的Meta分析CD14基因-159C/T多态性与变应性鼻炎(AR)易感性关系,为AR的发病机制及疾病预防提供理论依据。方法检索PubMed、EMBASE、Cochrane等国外数据库及中国期刊全文数据库、中国科技期刊数据库、中国生物医学文献数据库、万方数字...目的Meta分析CD14基因-159C/T多态性与变应性鼻炎(AR)易感性关系,为AR的发病机制及疾病预防提供理论依据。方法检索PubMed、EMBASE、Cochrane等国外数据库及中国期刊全文数据库、中国科技期刊数据库、中国生物医学文献数据库、万方数字期刊全文数据库等中文数据库中发表的CD14基因-159C/T多态性与变应性鼻炎易感性关系的病例对照研究。根据纳入和排除标准对文献进行筛选,用Jadad quantity对纳入的文献进行偏差评估和敏感性分析,用Revman5.3软件对数据进行处理。结果根据纳入和排除标准,共纳入9篇文献,共2319名受试者,其中病例组1195例,对照组1124例。Meta分析结果显示:优势基因模型下(CC vs CT+TT),组合OR值为0.74,95%CI为[0.61,0.90],P=0.002,差异有统计学意义;超显性基因模型下(CT vs CC+TT),联合OR值为1.12,95%CI为[0.95,1.32],P=0.18,差异无统计学意义;隐性基因模型下(TT vs CC+CT),联合OR值为1.14,95%CI为[0.95,1.38],P=0.15;等位基因(C对T),合并OR值为0.95,95%CI为[0.83,1.10],P=0.50,差异无统计学意义。表明与T等位基因相比,在a位点携带C等位基因不会增加AR的易感性。优势基因模型可能增加基因型CD14基因-159C/T的AR易感性,而隐性基因模型和超显性基因模型可能不会增加基因型CD14基因-159C/T的AR易感性。结论CD14基因-159C/T多态性与AR易感性无显著相关性。基因座中的基因型可能增加AR易感性的基因模型是优势基因模型。展开更多
基金Supported by grants from the Else Kr(o|¨)ner Fresenius-Stiftung to Hellerbrand C and the Deutsche Forschungsgemeinschaft (Schn 620/3-1) to Schnabl B
文摘AIM: Clinical and experimental data suggest that gut-derived endotoxins are an important pathogenic factors for progression of chronic liver disease. Recently, a C-T (-159)polymorphism in the promoter region of the CD14 gene was detected and found to confer increased CD14 expression and to be associated with advanced alcoholic liver damage. Here, we investigated this polymorphism in patients with less advanced alcoholic liver disease (ALD)and chronic hepatitis C virus (HCV) infection.METHODS: CD14 genotyping was performed by PCR-RFLP analysis in (a) 121 HCV patients, (b) 62 patients with alcohol-associated cirrhosis (Alc-Ci), (c) 118 individuals with heavy alcohol abuse without evidence of advanced liver damage (Alc-w/o Ci), and (d) 247 healthy controls.Furthermore, serum levels of soluble CD14 (sCD14) and transaminases were determined.RESULTS: The TT genotype was significantly more frequent in Alc-Ci compared to Alc-w/o Ci or controls (40.3% vs 23.7% or 24.0%, respectively). In Alc-w/o Ci,serum levels of transaminases did not differ significantly between patients with different CD14 genotypes. In HCV patients, TT-homozygotes had significantly higher sCD14 levels and sCD14 serum levels were significantly higher in patients with advanced fibrosis or cirrhosis. However,no association was found between CD14 genotypes and histological staging or grading.CONCLUSION: Considering serum transaminases as surrogate markers for alcoholic liver damage, the CD14 polymorphism seems to exhibit different effects during the course of ALD. Differences in genotype distribution between cirrhotic HCV patients and alcoholics and the known functional impact of this polymorphism on CD14 expression levels further indicate differences in the pathophysiological role of CD14 and CD14-mediated lipopolysaccharides signal transduction with regard to the stage as well as the type of the underlying liver disease.
文摘AIM: To investigate whether single-nucleotide polymor- phisms in the promoter regions of endotoxin-responsive genes CD14 C (-159) T is associated with chronic hepatitis B. METHODS: We obtained genomic DNA from 80 patients with established diagnosis of chronic hepatitis B and 126 healthy subjects served as a control population. The CD 14 C (-159) T polymorphism was investigated using an allele specific PCR method. RESULTS: Twenty seven percent of chronic hepatitis B patients and 75% of controls were heterozygous for CT genotype. The difference between the chronic hepatitis B and control groups was statistically significant [P < 0.0001; Odds ratio (OR) = 2.887; 95% CI: 1.609-5.178]. Twenty four point six percent of chronic hepatitis B and patients 12.3% of the control group were heterozygous for TT genotype. The difference between groups was not statistically significant (P = 0.256; OR = 0.658; 95% CI: 0.319-1.358). Forty eight point four percent of chronic hepatitis B patients and 12.7% of control were homozy- gote for CC genotype (P < 0.004; OR = 0.416; 95% CI: 0.229-0.755). The frequency of allele C was 61.9% and allele T was 38.1% in hepatitis B patients group. The frequency of allele C was 55.2% and allele T was 44.8% for the control group (P = 0.179; OR = 1.319; 95% CI: 0.881-1.977). CONCLUSION: The TT heterozygous genotype was not a risk factor for chronic hepatitis B. CC homozygote genotype is protective for hepatitis B. Lack of heterozy- gosis of genotype CT is a risk factor for chronic hepatitis B. Alleles C or T were not risk factors for chronic hepatitis B. These findings show the role of a single-nucleotide polymorphism at CD14/-159 on the development ofchronic hepatitis B. Endotoxin susceptibility may play a role in the pathogenesis of chronic hepatitis B.
文摘目的Meta分析CD14基因-159C/T多态性与变应性鼻炎(AR)易感性关系,为AR的发病机制及疾病预防提供理论依据。方法检索PubMed、EMBASE、Cochrane等国外数据库及中国期刊全文数据库、中国科技期刊数据库、中国生物医学文献数据库、万方数字期刊全文数据库等中文数据库中发表的CD14基因-159C/T多态性与变应性鼻炎易感性关系的病例对照研究。根据纳入和排除标准对文献进行筛选,用Jadad quantity对纳入的文献进行偏差评估和敏感性分析,用Revman5.3软件对数据进行处理。结果根据纳入和排除标准,共纳入9篇文献,共2319名受试者,其中病例组1195例,对照组1124例。Meta分析结果显示:优势基因模型下(CC vs CT+TT),组合OR值为0.74,95%CI为[0.61,0.90],P=0.002,差异有统计学意义;超显性基因模型下(CT vs CC+TT),联合OR值为1.12,95%CI为[0.95,1.32],P=0.18,差异无统计学意义;隐性基因模型下(TT vs CC+CT),联合OR值为1.14,95%CI为[0.95,1.38],P=0.15;等位基因(C对T),合并OR值为0.95,95%CI为[0.83,1.10],P=0.50,差异无统计学意义。表明与T等位基因相比,在a位点携带C等位基因不会增加AR的易感性。优势基因模型可能增加基因型CD14基因-159C/T的AR易感性,而隐性基因模型和超显性基因模型可能不会增加基因型CD14基因-159C/T的AR易感性。结论CD14基因-159C/T多态性与AR易感性无显著相关性。基因座中的基因型可能增加AR易感性的基因模型是优势基因模型。
