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细胞因子和细胞间黏附分子-1基因多态性对慢性胰腺炎易感性的影响。

Influence of cytokine and ICAM-1 gene polymorphisms on susceptibility to chronic pancreatitis.

作者信息

Howell W M, Pead P J, Shek F W, Rose-Zerilli M J, Armstrong T, Johnson C D, Fine D R, Iredale J P, Bateman A C

机构信息

The Pancreatic and Liver Fibrosis Research Groups, Divisions of Human Genetics, Allergy and Repair, University of Southampton, Southampton SO16 6YD, UK.

出版信息

J Clin Pathol. 2005 Jun;58(6):595-9. doi: 10.1136/jcp.2004.020842.

Abstract

AIMS

To test the hypothesis that single nucleotide polymorphisms (SNPs) within genes (or their promoter regions) encoding cytokines, growth factors, and intercellular adhesion molecules modulate the risk of development of chronic pancreatitis (CP).

METHODS

DNA was extracted from peripheral blood leucocytes or formalin fixed, paraffin wax embedded tissue from 53 patients with CP and 266 healthy controls. SNPs within the interleukin 1beta (IL-1beta), IL-6, IL-8, tumour necrosis factor alpha (TNFalpha) and vascular endothelial growth factor (VEGF) gene promoter regions and the transforming growth factor beta1 (TGFbeta1) and intercellular cell adhesion molecule 1 (ICAM-1) genes were genotyped by the amplification refractory mutation system polymerase chain reaction or 5' nuclease (Taqman) techniques. Patient-control comparisons were made using 2 x 2 contingency tables and chi2 analyses.

RESULTS

A non-significant decrease in the frequency of the IL-8 -251 AA genotype and a non-significant increase in the frequency of the ICAM-1 +469 GA genotype was seen in patients compared with controls. No associations were identified between SNPs in the promoter regions of the IL-1beta, IL-6, or TNFalpha proinflammatory cytokines genes or the TGFbeta1 and VEGF genes and susceptibility to CP.

CONCLUSIONS

This preliminary study suggests that genetic polymorphism within several cytokine genes is unlikely to influence susceptibility to CP, but the possible role of IL-8 and ICAM-1 polymorphisms in the development of this disease requires further investigation.

摘要

目的

检验以下假设,即编码细胞因子、生长因子和细胞间黏附分子的基因(或其启动子区域)内的单核苷酸多态性(SNP)会调节慢性胰腺炎(CP)的发病风险。

方法

从53例CP患者和266名健康对照者的外周血白细胞或福尔马林固定、石蜡包埋组织中提取DNA。通过扩增阻滞突变系统聚合酶链反应或5'核酸酶(Taqman)技术对白细胞介素1β(IL-1β)、IL-6、IL-8、肿瘤坏死因子α(TNFα)和血管内皮生长因子(VEGF)基因启动子区域以及转化生长因子β1(TGFβ1)和细胞间细胞黏附分子1(ICAM-1)基因内的SNP进行基因分型。使用2×2列联表和卡方分析进行患者与对照的比较。

结果

与对照组相比,患者中IL-8 -251 AA基因型频率有非显著性降低,ICAM-1 +469 GA基因型频率有非显著性升高。在IL-1β、IL-6或TNFα促炎细胞因子基因启动子区域以及TGFβ1和VEGF基因的SNP与CP易感性之间未发现关联。

结论

这项初步研究表明,几种细胞因子基因内的基因多态性不太可能影响CP易感性,但IL-8和ICAM-1多态性在该疾病发生中的可能作用需要进一步研究。

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