Objective To define the functional significance of IL-1 receptor antagonist (IL-1ra) gene polymorphism and to investigate, the production of IL-1ra by monocytes from individuals with different genotypes of IL-1.Method...Objective To define the functional significance of IL-1 receptor antagonist (IL-1ra) gene polymorphism and to investigate, the production of IL-1ra by monocytes from individuals with different genotypes of IL-1.Methods The genotype of IL-1ra was detected by polymerase chain reaction (PCR). Peripheral monocytes obtained from patients with immunoglobin A nephropathy (IgAN), Henoch-Schonlein purpura nephritis (HSPN) and normal subjects were matched in sex and age between the IL1RN-2 allele carriers and non-carriers. The secretion of IL-1ra, IL-1α and IL-1β in the supernatant of GM-CSF (10ng/ml) treated and untreated monocytes were measured by ELISA.Results The secretion of IL-1ra by monocytes stimulated with GM-CSF was significantly higher in the IL1RN-2 allele non-carriers than those of carriers both in IgAN (21.55±3.08 vs 13.85±2.24ng/ml, P<0.001) and HSPN (23.72±6.68 vs 12.67±2.24ng/ml, P<0.01) as well as in normal controls (20.29±1.45 vs 10.51±2.3ng/ml, P<0.001). All showed no significant differences in monocyte secretion of IL-1α and IL-1β by GM-CSF stimulation between the IL1RN-2 allele carriers and non-carriers. Conclusions These results indicate that a functional correlation of the IL1RN-2 allele and IL-1ra production is present in patients with IgAN and HSPN. This gene polymorphism control of IL-1ra production may contribute to the variety of clinical responses to inflammatory stimulation in individuals with different genotype of IL-1ra.展开更多
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
Objective：To explore the association of Chinese medicine constitution susceptibility to diabetic nephropathy（DN） and transforming growth factor（TGF）-β1（T869C） gene polymorphism.Methods：TGF-β1 gene polymorphi...Objective：To explore the association of Chinese medicine constitution susceptibility to diabetic nephropathy（DN） and transforming growth factor（TGF）-β1（T869C） gene polymorphism.Methods：TGF-β1 gene polymorphism detected with polymerase chain reaction-restriction fragment length polymorphism（PCRRFLP） was screened for 180 DN cases and 180 type 2 diabetic mellitus（T2DM） cases without combined DN. Patients with DN were surveyed epidemiologically with constitution in the Chinese medicine questionnaire （CCMQ）.Binary logistic regression analysis was utilized to study the correlation between nine types of Chinese medicine constitution and TGF-β1（T869C） gene polymorphisms.Results：The DN group has a higher frequency of TGF-β1（T869C） gene polymorphism than the T2DM group,and CC/CT genotypes than the T2DM group[CC,CT,TT（DN group）：88,87,5（cases） versus（T2DM group） 71,73,36（cases）,P0.05].The phlegm-dampness constitution,damp-heat constitution,and blood stasis constitution have correlations with TGF-β1 （T869C） gene polymorphism.Conclusion：Chinese medicine constitutions were associated with TGF-β1（T869C） gene polymorphism,a potential predictor of susceptibility to DN in T2DM patients.展开更多
目的:通过对IL-1受体拮抗剂(IL-1ra)基因多态性的分析,探讨IgA肾病(IgAN)的异质性以及新月体型IgAN与系统性小血管炎之间的联系。方法:随机选取200例IgAN患者、90例过敏紫癜性肾炎(HSPN)患者、45例微型多血管炎(MPA)患者及100例健康志...目的:通过对IL-1受体拮抗剂(IL-1ra)基因多态性的分析,探讨IgA肾病(IgAN)的异质性以及新月体型IgAN与系统性小血管炎之间的联系。方法:随机选取200例IgAN患者、90例过敏紫癜性肾炎(HSPN)患者、45例微型多血管炎(MPA)患者及100例健康志愿者。依据解放军肾脏病研究所拟定的分型标准,将IgAN分为六型。PCR法检测样本IL-1ra基因型。分析IL-1ra基因多态性与IgAN患者临床病理特征的联系及其在不同类型IgAN患者中的分布。分析IgAN总体、新月体型(Cres.)IgAN、HSPN、MPA不同组别间IL-1ra基因多态性的异同。结果:(1)IgAN、MPA患者IL1RN*2等位基因频率和携带率与正常对照组无统计学差异,HSPN患者IL1RN*2频率和携带率显著高于正常对照组(21.1% vs 12.0%,P<0.05;40.0% vs 24.0%,P<0.05)。(2)携带IL1RN*2的IgAN患者反复肉眼血尿发生率、肉眼血尿发作间期尿红细胞≥50万/ml发生率、新月体比例、细胞型/纤维细胞型新月体比例和毛细血管袢坏死发生率显著高于IL1RN*2不携带组(P<0.05)。(3)Cres.IgAN的IL1RN*2携带率(56.3%),显著高于其它类型IgAN及正常人群。(4)HSPN患者IL1RN*2携带组新月体比例、细胞型/纤维细胞型新月体比例以及毛细血管袢坏死发生率显著高于不携带组(P<0.05)。新月体比例≥15%组IL1RN*2携带率显著高于新月体比例<15%组。(6)新月体型IgAN患者IL1RN*2携带率,无论与HSPN总体还是与新月体比例≥15% HSPN患者相比,均无统计学差异;并且与后者数值非常接近(56.3% vs 57.7%)。结论:IL1RN*2等位基因与Cres.IgAN和HSPN的发生均有关。IL1RN*2高携带率可能是Cres.IgAN和HSPN共同的遗传背景之一。展开更多
目的：探讨IL-10基因启动子区域G-1082A、C-592A多态性与汉族人群IgA肾病（IgAN）发病间关系。方法：用SSP-PCR方法对180例IgA肾病（IgAN）患者和163例健康对照组IL-10基因启动子区域-1082、-592位点单核苷酸多态性进行分析。结果：-108...目的：探讨IL-10基因启动子区域G-1082A、C-592A多态性与汉族人群IgA肾病（IgAN）发病间关系。方法：用SSP-PCR方法对180例IgA肾病（IgAN）患者和163例健康对照组IL-10基因启动子区域-1082、-592位点单核苷酸多态性进行分析。结果：-1082位点IgA肾病患者AG/GG基因型频率显著高于正常对照组（为21.0% vs 11.7%,P〈0.05）;-1082位点G等位基因频率显著高于正常对照组（为11.0% vs 6.4%,P〈0.01）;携带有G等位基因者患IgA肾病危险性是携带有A等位基因者1.8倍,95%CI为1.12-3.20。-592位点IgA肾病患者AA、CA、CC基因型与正常对照组相比,无统计学差异（11.11% vs 16.56%;46.67% vs 51.53%;42.22% vs 31.90%,P〉0.05）;-592位点C等位基因频率与正常对照组相比,无统计学差异（32.21% vs 32.50%,P〉0.05）。结论：IL-10基因G-1082A是中国汉族人群IgA肾病患者的易感基因,携带G等位基因者患IgA肾病的危险性是携带A等位基因者的1.8倍。展开更多
文摘Objective To define the functional significance of IL-1 receptor antagonist (IL-1ra) gene polymorphism and to investigate, the production of IL-1ra by monocytes from individuals with different genotypes of IL-1.Methods The genotype of IL-1ra was detected by polymerase chain reaction (PCR). Peripheral monocytes obtained from patients with immunoglobin A nephropathy (IgAN), Henoch-Schonlein purpura nephritis (HSPN) and normal subjects were matched in sex and age between the IL1RN-2 allele carriers and non-carriers. The secretion of IL-1ra, IL-1α and IL-1β in the supernatant of GM-CSF (10ng/ml) treated and untreated monocytes were measured by ELISA.Results The secretion of IL-1ra by monocytes stimulated with GM-CSF was significantly higher in the IL1RN-2 allele non-carriers than those of carriers both in IgAN (21.55±3.08 vs 13.85±2.24ng/ml, P<0.001) and HSPN (23.72±6.68 vs 12.67±2.24ng/ml, P<0.01) as well as in normal controls (20.29±1.45 vs 10.51±2.3ng/ml, P<0.001). All showed no significant differences in monocyte secretion of IL-1α and IL-1β by GM-CSF stimulation between the IL1RN-2 allele carriers and non-carriers. Conclusions These results indicate that a functional correlation of the IL1RN-2 allele and IL-1ra production is present in patients with IgAN and HSPN. This gene polymorphism control of IL-1ra production may contribute to the variety of clinical responses to inflammatory stimulation in individuals with different genotype of IL-1ra.
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.
基金Supported by the National Natural Science Foundation of China(No.30801467) Zhejiang Provincial Natural Science Foundation of China(No.Y2080683)
文摘Objective：To explore the association of Chinese medicine constitution susceptibility to diabetic nephropathy（DN） and transforming growth factor（TGF）-β1（T869C） gene polymorphism.Methods：TGF-β1 gene polymorphism detected with polymerase chain reaction-restriction fragment length polymorphism（PCRRFLP） was screened for 180 DN cases and 180 type 2 diabetic mellitus（T2DM） cases without combined DN. Patients with DN were surveyed epidemiologically with constitution in the Chinese medicine questionnaire （CCMQ）.Binary logistic regression analysis was utilized to study the correlation between nine types of Chinese medicine constitution and TGF-β1（T869C） gene polymorphisms.Results：The DN group has a higher frequency of TGF-β1（T869C） gene polymorphism than the T2DM group,and CC/CT genotypes than the T2DM group[CC,CT,TT（DN group）：88,87,5（cases） versus（T2DM group） 71,73,36（cases）,P0.05].The phlegm-dampness constitution,damp-heat constitution,and blood stasis constitution have correlations with TGF-β1 （T869C） gene polymorphism.Conclusion：Chinese medicine constitutions were associated with TGF-β1（T869C） gene polymorphism,a potential predictor of susceptibility to DN in T2DM patients.
文摘目的:通过对IL-1受体拮抗剂(IL-1ra)基因多态性的分析,探讨IgA肾病(IgAN)的异质性以及新月体型IgAN与系统性小血管炎之间的联系。方法:随机选取200例IgAN患者、90例过敏紫癜性肾炎(HSPN)患者、45例微型多血管炎(MPA)患者及100例健康志愿者。依据解放军肾脏病研究所拟定的分型标准,将IgAN分为六型。PCR法检测样本IL-1ra基因型。分析IL-1ra基因多态性与IgAN患者临床病理特征的联系及其在不同类型IgAN患者中的分布。分析IgAN总体、新月体型(Cres.)IgAN、HSPN、MPA不同组别间IL-1ra基因多态性的异同。结果:(1)IgAN、MPA患者IL1RN*2等位基因频率和携带率与正常对照组无统计学差异,HSPN患者IL1RN*2频率和携带率显著高于正常对照组(21.1% vs 12.0%,P<0.05;40.0% vs 24.0%,P<0.05)。(2)携带IL1RN*2的IgAN患者反复肉眼血尿发生率、肉眼血尿发作间期尿红细胞≥50万/ml发生率、新月体比例、细胞型/纤维细胞型新月体比例和毛细血管袢坏死发生率显著高于IL1RN*2不携带组(P<0.05)。(3)Cres.IgAN的IL1RN*2携带率(56.3%),显著高于其它类型IgAN及正常人群。(4)HSPN患者IL1RN*2携带组新月体比例、细胞型/纤维细胞型新月体比例以及毛细血管袢坏死发生率显著高于不携带组(P<0.05)。新月体比例≥15%组IL1RN*2携带率显著高于新月体比例<15%组。(6)新月体型IgAN患者IL1RN*2携带率,无论与HSPN总体还是与新月体比例≥15% HSPN患者相比,均无统计学差异;并且与后者数值非常接近(56.3% vs 57.7%)。结论:IL1RN*2等位基因与Cres.IgAN和HSPN的发生均有关。IL1RN*2高携带率可能是Cres.IgAN和HSPN共同的遗传背景之一。
文摘目的：探讨IL-10基因启动子区域G-1082A、C-592A多态性与汉族人群IgA肾病（IgAN）发病间关系。方法：用SSP-PCR方法对180例IgA肾病（IgAN）患者和163例健康对照组IL-10基因启动子区域-1082、-592位点单核苷酸多态性进行分析。结果：-1082位点IgA肾病患者AG/GG基因型频率显著高于正常对照组（为21.0% vs 11.7%,P〈0.05）;-1082位点G等位基因频率显著高于正常对照组（为11.0% vs 6.4%,P〈0.01）;携带有G等位基因者患IgA肾病危险性是携带有A等位基因者1.8倍,95%CI为1.12-3.20。-592位点IgA肾病患者AA、CA、CC基因型与正常对照组相比,无统计学差异（11.11% vs 16.56%;46.67% vs 51.53%;42.22% vs 31.90%,P〉0.05）;-592位点C等位基因频率与正常对照组相比,无统计学差异（32.21% vs 32.50%,P〉0.05）。结论：IL-10基因G-1082A是中国汉族人群IgA肾病患者的易感基因,携带G等位基因者患IgA肾病的危险性是携带A等位基因者的1.8倍。
