Boiardi Luigi, Casali Bruno, Farnetti Enrico, Pipitone Nicolò, Nicoli Davide, Cantini Fabrizio, Macchioni Pierluigi, Bajocchi Gianluigi, Catanoso Maria Grazia, Pulsatelli Lia, Consonni Dario, Salvarani Carlo
Servizio di Reumatologia, Arcispedale S. Maria Nuova, Reggio Emilia, Italy.
J Rheumatol. 2006 Apr;33(4):703-8.
To assess the role of -174 G/C promoter polymorphism of interleukin 6 (IL-6) in the susceptibility to polymyalgia rheumatica (PMR). We also investigated whether this polymorphism modulates the circulating level of IL-6 and the risk of relapse/recurrence in a series of patients with PMR followed up prospectively.
A prospective study of 112 consecutive, untreated patients with isolated PMR (i.e., without evidence of giant cell arteritis) who were followed up for at least 24 months. This cohort represented all patients diagnosed over a 5-year period in one Italian rheumatological secondary referral center. Patients were monitored for clinical signs/symptoms and acute-phase reactants. All PMR patients and 112 population-based controls from the same geographic area were genotyped for IL-6 polymorphism at position -174 by molecular methods. IL-6 serum levels were measured in 67 PMR patients and 43 population-based controls.
The distribution of the G/C 174 genotype was similar in PMR patients and controls. No significant associations with IL-6 promoter polymorphism at position -174 were found when PMR patients with and without relapse/recurrence were compared. Controls homozygous for the C allele had higher serum IL-6 levels than the carriers of the G allele (4.5 +/- 3.7 pg/ml vs 1.8 +/- 2.1 pg/ml, p = 0.01). Patients homozygous for the allele C had significantly higher values of IL-6 during followup than patients carrying GC or GG genotypes. CC homozygosity was significantly more frequent in patients with persistently elevated levels of IL-6 than in those without. The presence of persistently elevated IL-6 levels, but not the CC genotype, was associated with an increased frequency of relapse/recurrence.
Our findings show that the 174 G/C promoter IL-6 polymorphism is not implicated in susceptibility to PMR. However, CC genotype characterized PMR patients with persistently elevated levels of IL-6 who are at higher risk of developing relapse/recurrence. A genetically modulated pattern of IL-6 production could affect the longterm outcome of patients with PMR.
评估白细胞介素6（IL-6）-174 G/C启动子多态性在风湿性多肌痛（PMR）易感性中的作用。我们还研究了这种多态性是否调节IL-6的循环水平以及一系列前瞻性随访的PMR患者的复发/再发风险。
对112例未经治疗的孤立性PMR患者（即无巨细胞动脉炎证据）进行前瞻性研究，随访至少24个月。该队列代表了意大利一个风湿病二级转诊中心5年内诊断的所有患者。对患者的临床症状/体征和急性期反应物进行监测。采用分子方法对所有PMR患者和来自同一地理区域的112名基于人群的对照者进行IL-6基因-174位点多态性基因分型。检测了67例PMR患者和43名基于人群的对照者的血清IL-6水平。
PMR患者和对照者中G/C 174基因型的分布相似。比较有复发/再发和无复发/再发的PMR患者时，未发现与-174位点IL-6启动子多态性有显著关联。C等位基因纯合的对照者血清IL-6水平高于G等位基因携带者（4.5±3.7 pg/ml对1.8±2.1 pg/ml，p = 0.01）。随访期间，C等位基因纯合的患者IL-6值显著高于携带GC或GG基因型的患者。IL-6水平持续升高的患者中CC纯合子的频率显著高于未升高者。IL-6水平持续升高与复发/再发频率增加相关，但CC基因型与复发/再发频率增加无关。
我们的研究结果表明，174 G/C启动子IL-6多态性与PMR易感性无关。然而，CC基因型在IL-6水平持续升高且复发/再发风险较高的PMR患者中具有特征性。IL-6产生受基因调节的模式可能影响PMR患者的长期预后。
