Boiardi Luigi, Casali Bruno, Nicoli Davide, Farnetti Enrico, Chen Qingquan, Macchioni Pierluigi, Catanoso Maria Grazia, Pulsatelli Lia, Meliconi Riccardo, Salvarani Carlo
Servizio di Reumatologia and Laboratorio di Biologia Molecolare, Azienda Ospedaliera Arcispedale S. Maria Nuova, Viale Umberto 1 N50, 42100 Reggio Emilia, Italy.
J Rheumatol. 2003 Oct;30(10):2160-4.
To examine potential associations of vascular endothelial growth factor (VEGF) gene polymorphisms with giant cell arteritis (GCA) and disease expression, in particular in patients with and without ischemic complications.
We enrolled 92 consecutive patients with biopsy-proven GCA residing in Reggio Emilia, Italy. Two hundred healthy blood donors from the same geographic area were selected as controls. All the GCA patients and controls were genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for 936 C/T and 634 C/G mutations and for an 18 bp insertion/deletion (I/D) polymorphism in the VEGF promoter region. In vitro release of VEGF by peripheral blood mononuclear cells (PBMC) was investigated by ELISA in controls homozygous for the polymorphisms studied.
The carriage rates of the alleles I and C634 were significantly more frequent in GCA patients than in controls (p = 0.025, OR 1.9, 95% CI 1.1-3.1 and p = 0.015, OR 2.1, 95% CI 1.1-3.6, respectively). The distribution of allele T936 was similar in GCA patients and controls. No significant differences in the distribution of the polymorphisms studied were observed in patients with ischemic manifestations compared to those without ischemic manifestations. Lipopolysaccharide (LPS)-stimulated VEGF production by PBMC from controls was higher in II homozygous compared to DD homozygous patients.
Our data indicate that carriers of C634 and I alleles are associated with susceptibility to developing GCA.
研究血管内皮生长因子（VEGF）基因多态性与巨细胞动脉炎（GCA）及其疾病表现之间的潜在关联，特别是在有或无缺血性并发症患者中的情况。
我们纳入了92例连续的经活检证实患有GCA的患者，他们居住在意大利雷焦艾米利亚。选择来自同一地理区域的200名健康献血者作为对照。所有GCA患者和对照均通过聚合酶链反应和等位基因特异性寡核苷酸技术对VEGF启动子区域的936 C/T和634 C/G突变以及18 bp插入/缺失（I/D）多态性进行基因分型。通过酶联免疫吸附测定法（ELISA）研究了在所研究多态性中纯合子对照外周血单个核细胞（PBMC）释放VEGF的情况。
GCA患者中I等位基因和C634的携带率明显高于对照组（p = 0.025，比值比1.9，95%置信区间1.1 - 3.1；p = 0.015，比值比2.1，95%置信区间1.1 - 3.6）。GCA患者和对照组中T936等位基因的分布相似。与无缺血表现的患者相比，有缺血表现的患者在所研究的多态性分布上没有显著差异。与DD纯合子患者相比，II纯合子对照的PBMC在脂多糖（LPS）刺激下产生的VEGF更高。
我们的数据表明，C634和I等位基因携带者与发生GCA的易感性相关。
