Staffordshire Rheumatology Centre, The Haywood, High Lane, Burslem, Stoke-on-Trent, Staffordshire, England, UK.
J Rheumatol. 2011 May;38(5):802-9. doi: 10.3899/jrheum.101095. Epub 2011 Mar 1.
To determine whether variants in the vascular endothelial growth factor A (VEGFA) gene are associated with ischemic heart disease (IHD) and/or myocardial infarction (MI) in patients with rheumatoid arthritis (RA), and whether there is evidence of a gene-smoking interaction.
PCR-RFLP assays were used to determine the genotypes of VEGFA single-nucleotide polymorphisms (SNP) including VEGFA-2578A/C (rs699947), -460C/T (rs833061), +405C/G (rs2010963), and +936C/T (rs3025039) in 418 subjects with RA. Smoking history was obtained on each patient, and IHD and MI status was recorded. Associations with IHD/MI were assessed using contingency tables and logistic regression analyses.
Strong linkage disequilibrium was detected among VEGFA-2578, -460, and +405. SNP located in the VEGFA promoter region (-2578, -460) were found to be associated with IHD and MI, whereas +405 and +936, in the 5'-untranslated region (UTR) and 3'-UTR, respectively, were not. Haplotype analysis suggested that the A/C/G haplotype was associated with increased risk of IHD (OR 2.37, 95% CI 1.22-4.62) and MI (OR 4.10, 95% CI 1.45-11.49). Smoking was also independently associated with IHD and MI, and evidence of interaction between smoking and the VEGFA promoter SNP was found. Multivariate analyses indicated that the strongest associations with IHD and MI were due to the combined effect of the VEGFA-2578 A allele and smoking (OR 3.52 and 7.11, respectively), independent of risk factors such as age, sex, diabetes, C-reactive protein, hypercholesterolemia, and hypertension.
Interaction between smoking and polymorphism in the VEGFA gene is associated with IHD and MI in patients with RA.
确定血管内皮生长因子 A（VEGFA）基因中的变异是否与类风湿关节炎（RA）患者的缺血性心脏病（IHD）和/或心肌梗死（MI）相关，以及是否存在基因-吸烟相互作用的证据。
使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析确定了 418 例 RA 患者中 VEGFA 单核苷酸多态性（SNP）包括 VEGFA-2578A/C（rs699947）、-460C/T（rs833061）、+405C/G（rs2010963）和+936C/T（rs3025039）的基因型。每位患者均获得吸烟史，并记录 IHD 和 MI 状况。使用列联表和逻辑回归分析评估与 IHD/MI 的相关性。
检测到 VEGFA-2578、-460 和+405 之间存在强连锁不平衡。位于 VEGFA 启动子区域的 SNP（-2578、-460）与 IHD 和 MI 相关，而位于 5'-非翻译区（UTR）和 3'-UTR 的+405 和+936 则没有。单体型分析表明，A/C/G 单体型与 IHD（OR 2.37，95%CI 1.22-4.62）和 MI（OR 4.10，95%CI 1.45-11.49）的风险增加相关。吸烟也与 IHD 和 MI 独立相关，并且发现了吸烟与 VEGFA 启动子 SNP 之间相互作用的证据。多变量分析表明，与 IHD 和 MI 最强的关联是由于 VEGFA-2578 A 等位基因和吸烟的共同作用（OR 分别为 3.52 和 7.11），独立于年龄、性别、糖尿病、C 反应蛋白、高胆固醇血症和高血压等危险因素。
吸烟与 VEGFA 基因多态性的相互作用与 RA 患者的 IHD 和 MI 相关。
