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慢性阻塞性肺疾病患者环氧化酶-2 基因(G-765C)的功能多态性。

Functional polymorphism of cyclooxygenase-2 gene (G-765C) in chronic obstructive pulmonary disease patients.

机构信息

Department of Pneumology and Allergology, Medical University of Lodz, Kopcińskiego 22, 90-153 Lodz, Poland.

出版信息

Mol Biol Rep. 2012 Mar;39(3):2163-7. doi: 10.1007/s11033-011-0964-2. Epub 2011 Jun 8.

DOI:10.1007/s11033-011-0964-2
PMID:21655952
Abstract

Cyclooxygenase two (COX-2) is an important enzyme metabolizing arachidonic acid. In contrast to constitutive cyclooxygenase one (COX-1), COX-2 is induced by proinflammatory factors. Polymorphism -765 G/C in COX-2-encoding gene promoter is associated with development of Alzheimer's disease, depression, carcinoma of the pancreas in smokers, breast cancer and rheumatoid arthritis. It is interesting whether the -765 G/C polymorphism in COX-2-encoding gene promoter can be associated with COPD, a disease which is inflammatory in character. It is highly probable as the breast and pancreas cancers, whose associations with the analyzed polymorphism have been studied, are smoking-dependent tumors. Additionally, tobacco smoke has been demonstrated to induce COX-2 in the lungs. The study group consisted of 122 COPD patients (48 females, 74 males). The control group consisted of 149 healthy nonsmoking subjects (83 females, 66 males). Polymerase chain reaction/restriction fragment length polymorphism was used for genotyping. A statistically significant difference in genotype distribution was observed as a result of the comparison between healthy subjects and patients with COPD. The distribution of alleles in both groups conformed with Hardy-Weinberg equilibrium. In the group of COPD patients, GG allele was found in 79 subjects, GC in 36, and CC in 7 subjects (F = 0.094, P = 0.296927); in the control group, 73 subjects had GG allele, 68--GC and 8--CC (F = 0.12728, P = 0.120265). The allele frequency revealed differences between those groups, attaining the level of statistical significance (χ(2) = 29.043, df = 2, P = 0.0000. The carriers of -765 G allele are at 1.53-fold higher risk of developing COPD. The presence of GG genotype does not increase significantly the risk of the disease. It is also noteworthy that the carriers of CC or GC genotypes are at significantly lower risk of developing COPD than the group of subjects with GG genotype.

摘要

环氧化酶 2(COX-2)是一种代谢花生四烯酸的重要酶。与组成型环氧化酶 1(COX-1)不同,COX-2 由促炎因子诱导。COX-2 编码基因启动子中的 -765 G/C 多态性与阿尔茨海默病、抑郁症、吸烟者胰腺癌、乳腺癌和类风湿关节炎的发展有关。有趣的是,COX-2 编码基因启动子中的 -765 G/C 多态性是否与 COPD 有关,COPD 是一种具有炎症特征的疾病。这是很有可能的,因为乳腺癌和胰腺癌的发生与分析的多态性有关,这些癌症是与吸烟有关的肿瘤。此外,烟草烟雾已被证明能在肺部诱导 COX-2。研究组包括 122 例 COPD 患者(48 名女性,74 名男性)。对照组包括 149 名健康不吸烟的受试者(83 名女性,66 名男性)。采用聚合酶链反应/限制性片段长度多态性进行基因分型。通过对健康受试者和 COPD 患者的比较,观察到基因型分布存在统计学差异。两组的等位基因分布均符合哈迪-温伯格平衡。在 COPD 患者组中,GG 等位基因在 79 例中,GC 在 36 例中,CC 在 7 例中(F = 0.094,P = 0.296927);在对照组中,73 例有 GG 等位基因,68 例为 GC,8 例为 CC(F = 0.12728,P = 0.120265)。两组间的等位基因频率存在差异,达到统计学意义(χ(2) = 29.043,df = 2,P = 0.0000。-765 G 等位基因携带者患 COPD 的风险增加 1.53 倍。GG 基因型的存在并不能显著增加疾病的风险。同样值得注意的是,CC 或 GC 基因型的携带者患 COPD 的风险明显低于 GG 基因型的携带者。

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Eklem Hastalik Cerrahisi. 2011;22(1):22-7.
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The functional -765G→C polymorphism of the COX-2 gene may reduce the risk of developing crohn's disease.COX-2 基因的功能性-765G→C 多态性可能降低克罗恩病的发病风险。
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Cyclooxygenase-2 gene and lung carcinoma risk.环氧化酶-2 基因与肺癌风险。
基于生物信息学分析鉴定慢性阻塞性肺疾病差异表达基因及信号通路。
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A case-control study and meta-analysis reveal the association between COX-2 G-765C polymorphism and primary end-stage hip and knee osteoarthritis.一项病例对照研究及荟萃分析揭示了COX-2基因G-765C多态性与原发性终末期髋膝关节骨关节炎之间的关联。
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