Instituto de Parasitología y Biomedicina López-Neyra, C.S.I.C., Granada, Spain.
Clin Exp Rheumatol. 2011 Jul-Aug;29(4):681-8. Epub 2011 Aug 31.
Visfatin is an adipokine encoded by the NAMPT (PBEF1) gene. In this study we assessed the potential association of two NAMPT gene polymorphisms with disease susceptibility and cardiovascular (CV) risk in patients with rheumatoid arthritis (RA).
A total of 1,395 patients fulfilling the 1987 ACR classification criteria for RA and 1,230 matched controls, were genotyped for the NAMPT rs9770242 and rs59744560 gene polymorphisms, located within the proximal promoter, using predesigned TaqMan single nucleotide polymorphism genotyping assay. Also, HLA-DRB1 genotyping was performed using molecular based methods. In a second step, 1,196 patients in whom full information was available were assessed to determine the influence of NAMPT rs9770242 and rs59744560 polymorphisms in the development of CV events. Also, the potential influence of these polymorphisms in the development of subclinical atherosclerosis was assessed in a subgroup of patients with no history of CV events by brachial artery reactivity to determine flow-mediated endothelium-dependent and endothelium-independent vasodilatation (n=125) and by B-mode ultrasonography to determine the carotid artery intima-media thickness (n=105).
No statistically significant differences in the allele or genotype frequencies for the NAMPT gene polymorphisms between RA patients and controls were found. A modest non significant lower frequency of the minor allele G of rs9770242 polymorphism was observed among patients with CV disease (20.62%) compared to those without CV disease (22.83%) (p=0.39). Also, a slight nonsignificant lower frequency of the minor allele T of rs59744560 polymorphism in patients with CV events (9.81%) compared with those RA patients who did not experience CV disease (13.07%) (p=0.11) was observed. Likewise, no significant association between the NAMPT polymorphisms with surrogate markers of subclinical atherosclerosis was found in patients with RA.
NAMPT rs9770242 and rs59744560 polymorphisms are not markers of disease susceptibility and CV disease in RA.
内脏脂肪素是由 NAMPT（PBEF1）基因编码的脂肪因子。本研究评估了 NAMPT 基因两个多态性与类风湿关节炎（RA）患者疾病易感性和心血管（CV）风险的潜在关联。
共纳入 1395 例符合 1987 年 ACR 分类标准的 RA 患者和 1230 例匹配对照者，采用预设计的 TaqMan 单核苷酸多态性基因分型检测方法，对位于近端启动子内的 NAMPT rs9770242 和 rs59744560 基因多态性进行基因分型。此外，采用基于分子的方法进行 HLA-DRB1 基因分型。在第二步中，对 1196 例信息完整的患者进行评估，以确定 NAMPT rs9770242 和 rs59744560 多态性对 CV 事件发生的影响。此外，通过评估无 CV 事件史患者的肱动脉反应性来确定这些多态性对亚临床动脉粥样硬化发生的潜在影响，以确定血流介导的内皮依赖性和非内皮依赖性血管舒张（n=125），并通过 B 型超声检查来确定颈动脉内膜中层厚度（n=105）。
未发现 RA 患者和对照组之间 NAMPT 基因多态性的等位基因或基因型频率存在统计学显著差异。与无 CV 疾病的患者（22.83%）相比，CV 疾病患者（20.62%）中 NAMPT rs9770242 多态性的次要等位基因 G 的频率略低，但无统计学意义（p=0.39）。此外，与未发生 CV 疾病的 RA 患者（13.07%）相比，CV 事件患者（9.81%）中 rs59744560 多态性的次要等位基因 T 的频率略低，但无统计学意义（p=0.11）。同样，在 RA 患者中，也未发现 NAMPT 多态性与亚临床动脉粥样硬化的替代标志物之间存在显著关联。
NAMPT rs9770242 和 rs59744560 多态性不是 RA 患者疾病易感性和 CV 疾病的标志物。
