Balistreri Carmela Rita, Bonfigli Anna Rita, Boemi Massimo, Olivieri Fabiola, Ceriello Antonio, Genovese Stefano, Franceschi Claudio, Spazzafumo Liana, Fabietti Paolo, Candore Giuseppina, Caruso Calogero, Lio Domenico, Testa Roberto
Department of Pathobiology and Medical and Forensic Biotechnologies, University of Palermo, Tukory's Street 211, 90134 Palermo, Italy.
Metabolic Diseases and Diabetology Unit, Italian National Research Center on Aging (INRCA), Ancona, Italy.
Mediators Inflamm. 2014;2014:973139. doi: 10.1155/2014/973139. Epub 2014 Apr 2.
T2DM is today considered as world-wide health problem, with complications responsible of an enhanced mortality and morbidity. Thus, new strategies for its prevention and therapy are necessary. For this reason, the research interest has focused its attention on TLR4 and its polymorphisms, particularly the rs4986790. However, no conclusive findings have been reported until now about the role of this polymorphism in development of T2DM and its complications, even if a recent meta-analysis showed its T2DM association in Caucasians. In this study, we sought to evaluate the weight of rs4986790 polymorphism in the risk of the major T2DM complications, including 367 T2DM patients complicated for the 55.6%. Patients with A/A and A/G TLR4 genotypes showed significant differences in complication's prevalence. In particular, AG carriers had higher risk prevalence for neuropathy (P = 0.026), lower limb arteriopathy (P = 0.013), and the major cardiovascular pathologies (P = 0.017). Their cumulative risk was significant (P = 0.01), with a threefold risk to develop neuropathy, lower limb arteriopathy, and major cardiovascular events in AG cases compared to AA cases. The adjusted OR for the confounding variables was 3.788 (95% CI: 1.642-8.741). Thus, the rs4986790 polymorphism may be an indicative of prevalence of complications in T2DM patients.
如今,2型糖尿病被视为全球性的健康问题,其并发症会导致死亡率和发病率上升。因此,有必要采取新的预防和治疗策略。出于这个原因,研究兴趣集中在Toll样受体4(TLR4)及其多态性上,特别是rs4986790。然而,到目前为止,关于这种多态性在2型糖尿病及其并发症发展中的作用尚未有确凿的研究结果报道,尽管最近的一项荟萃分析表明它与白种人中的2型糖尿病有关联。在本研究中,我们试图评估rs4986790多态性在主要2型糖尿病并发症风险中的影响,研究对象包括367例2型糖尿病患者,其中55.6%出现了并发症。TLR4基因A/A和A/G基因型的患者在并发症患病率上存在显著差异。特别是,AG基因型携带者患神经病变(P = 0.026)、下肢动脉病变(P = 0.013)和主要心血管疾病(P = 0.017)的风险更高。他们的累积风险具有统计学意义(P = 0.01),与AA基因型患者相比,AG基因型患者发生神经病变、下肢动脉病变和主要心血管事件的风险增加了两倍。经混杂变量调整后的比值比为3.788(95%置信区间:1.642 - 8.741)。因此,rs4986790多态性可能是2型糖尿病患者并发症患病率的一个指标。