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溃疡性结肠炎与细胞因子基因多态性的相关研究
中文摘要

 目的 测定溃疡性结肠炎(Ulcerative Colitis,UC)患者细胞因子(Cytokin,CK)的基因多态性及血清学水平,探讨细胞因子基因多态性与溃疡性结肠炎的关系。 方法 采用序列特异性引物聚合酶链反应(PCR-SSP)的分析方法,检测了60例明确诊断的溃疡性结肠炎患者和60例健康人肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)、白细胞介素-6(Interleukin-6,IL-6)、转化生长因子-β(Transforming growth factor-β₁,TGF-β₁)、白细胞介素-10(Interleukin-10,IL-10)、干扰素-γ(Interferon-γ,IFN-γ)和白细胞介素-1(Interleukin-1,IL-1)的基因多态性。检测的位点包括:TNF-α-308、IL-6-174,IL-1α-899、IL-1β+3962, IFN-γ+874、IL-10-1082、 IL-10-819、IL-10-592, TGF-β₁密码子10和密码子25上的特殊位点;同时采用酶联免疫吸附试验(ELISA)检测TNF-α、IL-6、TGF-β、IL-10和IFN-γ细胞因子血清水平。 结果 1 IL-1β+3962位点基因型频率及等位基因频率UC患者与对照组比较差异有统计学意义(P< 0.05)。 2 UC患者中全结肠病变者TNF-α-308G/G基因型出现的频率比左半结肠组和直肠组病变的患者明显增高,统计学差异具有显著性(P<0.05) 3 TNF-α-308、IL-6-174,IFN-γ+874、IL-1α-899位点基因型频率及等位基因频率UC患者与正常人群比较无显著差别(P>0.05)。 4 IL-10-1082、IL-10-819,IL-10-592及TGF-β密码子10和密码子25上的特殊位点的基因分泌型频率及等位基因频率UC组与对照组之间差异无统计学意义(P>0.05)。 5 IL-6-174,IL-1α-899、IL-1β+3962,IFN-γ+874、TGF-β、IL-10各基因型在UC组不同发病部位之间的分布差异无显著性(P>0.05)。 6 UC组与对照组间虽TNF-α-308、IL-6-174,IFN-γ+874和IL-10-1082、 IL-10-819,IL-10-592位点基因型频率及等位基因频率比较无显著差别,但对应外周血细胞因子水平有显著差异(P<0.05)。活动期UC患者TNF-α、IL-6、IFN-γ和IL-10血清浓度明显高于正常对照组。 结论 IL-1β+3962位点基因多态性可能与UC发病有关。全结肠患病的患者比直肠组和左半结肠组的患者更易表达TNF-α-308G/G基因型,TNF-α-308G/G基因型可能与UC患者疾病发展和病变范围有关。TNF-α-308、IL-6-174、IFN-γ+874、 IL-1α-899、IL-10和TGF-β基因多态性可能与UC发病的易感性无关。TNF-α-308, IL-6-174,IFN-γ+874和IL-10-1082、IL-10-819,IL-10-592位点的基因多态性可能不是UC患者外周血细胞因子水平的决定性因素。 关键词 溃疡性结肠炎;细胞因子;基因多态性

英文摘要

 Objective To investigate the gene polymorphisms and serum levels of Cytokin in patients with ulcerative colitis .And analysis the relationship of UC and gene polymorphism. Methods 60 UC patients and 60 healthy controls, were studied. DNA was isolated from peripheral-blood: The specific gene polymorphisms that were probed for included : Tumor necrosis factor-alpha (TNF-α)、Interleukin-6 (IL-6)、 Transforming growth factor-β (TGF-β)、 Interleukin-10 (IL-10 ) Interferon-γ (IFN-γ) and Interleukin-1 (IL-1 )The sites of TNF-α at -308 (G/A)、IFN gamma at +874 (T/A)、 IL-1 alpha at-899(C/T) 、IL-1 beta at C/T +3962 、TGFbeta 1 at codon 10 (C/T) and codon 25 (G/C), IL-10 at -1082 (G/A), -819 (C/T) and -592 (C/A)and IL-6 at +174 (G/C) were studied by Sequence- Specific Primers polymerase chain reaction (PCR-SSP) using the Cytokine Genotyping Tray kit according with the manufacturer specifications And the serum levels of TNF-α、IL-6、TGF-β、IL-10、IFN-γ were assayed by ELISA. Results 1 The genotype frequency and allelic frequency of IL-1β+3962 in UC had significant difference compared with that in normal control cases (P<0.05 ) 2 The genetype of TNF-α-308G/G appeared in Pancolitis was more frequently than that appeared in proctitis and left-sided colitis (P<0.05 ) . 3 The genotype frequency and allelic frequency of TNF-α-308 、IL-6-174、 IFN-γ+874 and IL-1α-899 in UC patients had no significant difference compared with that in normal control cases (P>0.05 ) . 4 The genotypes frequency and allele frequency of IL-10-1082、 IL-10-819、 IL-10-592、TGFbeta 1 variants at codon 10 (C/T) and codon 25 (G/C) in UC had no significant difference compared with that in normal control cases. (p>0.05 ) 5 Each genotypes frequency of IL-6-174、IL-1α-899、IL-1β+3962、IFN-γ+874、 IL-10 and TGF-β had no significant difference among three regionals. (P>0.05 ) 6、The genotype frequency and allelic frequency of TNF-α-308、IL-6-174、 IFN-γ+874、 IL-10-1082、 IL-10-819 and IL-10 -592 had no significant difference compared with that in normal control cases (P>0.05 ) ,but the level of serum TNF -α、 IL-6 、 IFN-γ and IL-10 in active UC had significant difference compared with that in normal control cases (P<0.05). The level of serum TNF -α、IL - 6 、 IFN-γ and IL-10 in active UC was mach higher than that of control group. Conclusion The polymorphisms at IL-1 β+3962 may have influences on the susceptibility to UC. Patients with proctitis and left-sided colitis were more likely to express the TNF-α -308G/G (low producer) genotype. Genotype TNF-α-308 G/G may correlate with extent and development of the disease. No statistical relationship was observed between the gene polymorphisms of TNF-α-308 、IL-6-174 、IFN-γ+874、 IL-1α-899 、TGF-β and IL-10 the susceptibility to UC .The polymorphisms at TNF-α-308、IL-6-174、IFN-γ+874 、IL-10-1082、IL-10-819 and IL-10-592 may not be the determinants of serum level in UC patients. Key words Ulcerative colitis; Cytokin ; Gene polymorphisms

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