Evidences of +896 A/G TLR4 Polymorphism as an Indicative of Prevalence of Complications in T2DM Patients

Author:

Balistreri Carmela Rita1,Bonfigli Anna Rita2ORCID,Boemi Massimo2,Olivieri Fabiola34,Ceriello Antonio56,Genovese Stefano7,Franceschi Claudio8,Spazzafumo Liana9,Fabietti Paolo9,Candore Giuseppina1,Caruso Calogero1ORCID,Lio Domenico1,Testa Roberto10ORCID

Affiliation:

1. Department of Pathobiology and Medical and Forensic Biotechnologies, University of Palermo, Tukory’s Street 211, 90134 Palermo, Italy

2. Metabolic Diseases and Diabetology Unit, Italian National Research Center on Aging (INRCA), Ancona, Italy

3. Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy

4. Center of Clinical Pathology and Innovative Therapy, Italian National Research Center on Aging (INRCA), Ancona, Italy

5. Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

6. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain

7. Department of Cardiovascular and Metabolic Diseases, IRCCS Gruppo Multimedica, Sesto San Giovanni (MI), Italy

8. Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, CNR-ISOF and IRCCS Neuroscience, Bologna, Italy

9. Biostatistical Center, Italian National Research Center on Aging (INRCA), Ancona, Italy

10. Experimental Models in Clinical Pathology, Italian National Research Center on Aging (INRCA), Ancona, Italy

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.

Funder

Palermo University

Publisher

Hindawi Limited

Subject

Cell Biology,Immunology

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