Bown Matthew J, Lloyd Geraint M, Sandford Rebecca M, Thompson John R, London Nicholas J M, Samani Nilesh J, Sayers Robert D
Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
J Vasc Surg. 2007 Oct;46(4):687-93. doi: 10.1016/j.jvs.2007.06.025.
Abdominal aortic aneurysms (AAA) are caused by inflammatory processes in the wall of the aorta resulting in degradation of structural proteins. This inflammatory process is mediated, in part, by cytokines, and interleukin-10 (IL-10) is a predominantly anti-inflammatory cytokine. A single nucleotide polymorphism in the promoter region of the IL-10 gene that affects transcription has been associated with AAA in a small study. The aim of this study was to determine whether this polymorphism is associated with AAA and also examine its effect on the growth of small AAA.
A case control study was performed. A total of 389 patients with AAA and 404 healthy controls were recruited. IL-10-1082 polymorphisms were determined by polymerase chain reaction-based methods. In the case of patients with small AAA (<5.5 cm), serial size measurements were recorded to determine mean growth rate. There was a statistically significant difference both in allele and genotype frequencies between the case and control groups with the IL-10-1082 'A' allele being more common in the AAA group (P = .006). In the AAA group, genotype frequencies were as follows: GG 84, GA 201, and AA 104. In the control group, the genotype frequencies were GG 118, GA 205, and AA 81. The odds ratio for the 'A' allele as a risk factor for AAA was 1.50 (95% confidence interval 1.09 to 2.07). Regression modeling revealed that the IL-10-1082 genotype was, however, not independently associated with AAA if age, tobacco use, hypertension, and history of coronary or peripheral artery disease was taken into account. There was a trend towards lower plasma IL-10 level in IL-10 AA carriers, but the IL-10 'A' allele did not have any discernible effect on the growth of small AAA.
This study demonstrates that the IL-10-1082 'A' allele is associated with AAA, although this association is likely to be secondary to an association between IL-10-1082 genotype and other markers of cardiovascular disease rather than AAA per se.
腹主动脉瘤(AAA)由主动脉壁的炎症过程引起,导致结构蛋白降解。这种炎症过程部分由细胞因子介导,而白细胞介素-10(IL-10)是一种主要的抗炎细胞因子。一项小型研究发现,IL-10基因启动子区域影响转录的单核苷酸多态性与AAA有关。本研究的目的是确定这种多态性是否与AAA相关,并研究其对小型AAA生长的影响。
进行了一项病例对照研究。共招募了389例AAA患者和404名健康对照。采用基于聚合酶链反应的方法确定IL-10 -1082多态性。对于小型AAA(<5.5 cm)患者,记录连续的尺寸测量值以确定平均生长率。病例组和对照组之间的等位基因和基因型频率存在统计学显著差异,IL-10 -1082“A”等位基因在AAA组中更常见(P = .006)。在AAA组中,基因型频率如下:GG 84例,GA 201例,AA 104例。在对照组中,基因型频率为GG 118例,GA 205例,AA 81例。“A”等位基因作为AAA危险因素的比值比为1.50(95%置信区间1.09至2.07)。然而,回归模型显示,如果考虑年龄、吸烟、高血压以及冠状动脉或外周动脉疾病史,IL-10 -1082基因型与AAA并非独立相关。IL-10 AA携带者的血浆IL-10水平有降低趋势,但IL-10“A”等位基因对小型AAA的生长没有任何明显影响。
本研究表明,IL-10 -1082“A”等位基因与AAA相关,尽管这种关联可能继发于IL-10 -1082基因型与其他心血管疾病标志物之间的关联,而非AAA本身。