Biscetti Federico, Porreca Carlo Filippo, Bertucci Flavio, Straface Giuseppe, Santoliquido Angelo, Tondi Paolo, Angelini Flavia, Pitocco Dario, Santoro Luca, Gasbarrini Antonio, Landolfi Raffaele, Flex Andrea
Institute of Rheumatology and Affine Sciences, Catholic University School of Medicine, Rome, Italy.
Acta Diabetol. 2014 Dec;51(6):1025-32. doi: 10.1007/s00592-014-0664-1. Epub 2014 Oct 17.
Osteoprotegerin (OPG) is a secretory glycoprotein that belongs to the tumor necrosis factor receptor family and plays a role in atherosclerosis. OPG has been hypothesized to modulate vascular functions; however, its role in mediating atherosclerosis is controversial. Epidemiological data in patients with cardiovascular disease (CVD) indicate that OPG serum levels are associated with several inflammatory markers, myocardial infarction events, and calcium scores, suggesting that OPG may be causative for CVD.
The present study aimed to evaluate whether the OPG gene (TNFRSF11B) polymorphisms are involved in the development of peripheral arterial occlusive disease (PAOD) and critical limb ischemia (CLI) in patients with type 2 diabetes. This genetic association study included 402 diabetic patients (139 males and 263 females) with peripheral arterial occlusive disease and 567 diabetic subjects without peripheral arterial occlusive disease (208 males and 359 females). The T245G, T950C, and G1181C polymorphisms of the OPG gene were analyzed by polymerase chain reaction and restriction fragment length polymorphism.
We found that the T245G, T950C, and G1181C gene polymorphisms of the OPG gene were significantly (27.9 vs. 12.2 %, P < 0.01; 33.6 vs. 10.4 %, P < 0.01 and 24.4 vs. 12.7 %, P < 0.01, respectively) and independently (adjusted OR 4.97 (3.12-6.91), OR 7.02 (4.96-11.67), and OR 2.85 (1.95-4.02), respectively) associated with PAOD. We also found that these three polymorphisms act synergistically in patients with PAOD and are associated with different levels of risk for PAOD and CLI, depending on the number of high-risk genotypes carried concomitantly by a given individual.
The TNFRSF11B gene polymorphisms under study are associated with PAOD, and synergistic effects between these genotypes might be potential markers for the presence and severity of atherosclerotic disorders.
骨保护素（OPG）是一种分泌性糖蛋白，属于肿瘤坏死因子受体家族，在动脉粥样硬化中发挥作用。有人提出OPG可调节血管功能；然而，其在介导动脉粥样硬化中的作用存在争议。心血管疾病（CVD）患者的流行病学数据表明，OPG血清水平与多种炎症标志物、心肌梗死事件和钙评分相关，提示OPG可能是CVD的病因。
本研究旨在评估OPG基因（TNFRSF11B）多态性是否参与2型糖尿病患者外周动脉闭塞性疾病（PAOD）和严重肢体缺血（CLI）的发生。这项基因关联研究纳入了402例患有外周动脉闭塞性疾病的糖尿病患者（男性139例，女性263例）和567例无外周动脉闭塞性疾病的糖尿病受试者（男性208例，女性359例）。通过聚合酶链反应和限制性片段长度多态性分析OPG基因的T245G、T950C和G1181C多态性。
我们发现，OPG基因的T245G、T950C和G1181C基因多态性与PAOD显著相关（分别为27.9%对12.2%，P<0.01；33.6%对10.4%，P<0.01；24.4%对12.7%，P<0.01）且独立相关（调整后的OR分别为4.97（3.12 - 6.91）、7.02（4.96 - 11.67）和2.85（1.95 - 4.02））。我们还发现，这三种多态性在PAOD患者中具有协同作用，并且根据个体同时携带的高危基因型数量，与PAOD和CLI的不同风险水平相关。
所研究的TNFRSF11B基因多态性与PAOD相关，这些基因型之间的协同效应可能是动脉粥样硬化疾病存在和严重程度的潜在标志物。
