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Evidences of +896 A/G TLR4 polymorphism as an indicative of prevalence of complications in T2DM patients.

ABSTRACT: 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.

SUBMITTER: Balistreri CR

PROVIDER: S-EPMC3996297 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Evidences of +896 A/G TLR4 polymorphism as an indicative of prevalence of complications in T2DM patients.

Balistreri Carmela Rita CR Bonfigli Anna Rita AR Boemi Massimo M Olivieri Fabiola F Ceriello Antonio A Genovese Stefano S Franceschi Claudio C Spazzafumo Liana L Fabietti Paolo P Candore Giuseppina G Caruso Calogero C Lio Domenico D Testa Roberto R

Mediators of inflammation 20140402

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 it ...[more]

PMID: 24803744

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Project description:To assess the variations in pulmonary function and vascular endothelial function in their early stages (without related complications). A total of 162 type 2 diabetes mellitus (T2DM) patients without diabetes complications and 55 healthy people were selected, comprising the T2DM group and the control group, respectively, to evaluate changes in vascular endothelial function and lung function and determine the correlation between them. In this study, the T2DM group exhibited significantly lower pulmonary function than that of the control group (P < 0.05). The T2DM group also showed significantly lower flow-mediated dilation (FMD) and nitric oxide (NO) (P < 0.05) than those of the control group. Pulmonary functional indexes correlated positively with FMD and NO (P < 0.05) and correlated negatively with endothelin-1 (ET-1) (P < 0.05). FMD and NO correlated negatively with diabetes duration/HbA1c (P < 0.05), whereas ET-1 correlated positively with glycosylated hemoglobinA1c (HbA1c)/diabetes duration (P < 0.05). Pulmonary functional indexes negatively correlated with HbA1c/diabetes duration (P < 0.05). Multiple linear regression was used to analyze the relationship between vascular endothelial function indexes (FMD, ET-1, and NO) and pulmonary functional indexes. The results indicated that each vascular endothelial function index (FMD, ET-1, and NO) was significantly correlated with the pulmonary functional index (P < 0.05). The patients with T2DM presented changes in the subclinical vascular endothelial and pulmonary function. They also had impaired vascular endothelial functions, which were characterized by reduced vascular endothelial function relative to those of healthy people. Regulating glycemia may improve vascular endothelial and pulmonary functions. Moreover, microvascular lesions in preclinical stages, vascular endothelial function indexes (FMD, ET-1, and NO) were valid predictors of alterations in pulmonary function in T2DM patients without related complications.Clinical trial registrationClinicalTrials.gov, identifier NCT03575988.

Dataset Information

Evidences of +896 A/G TLR4 polymorphism as an indicative of prevalence of complications in T2DM patients.

Publications

Evidences of +896 A/G TLR4 polymorphism as an indicative of prevalence of complications in T2DM patients.

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