Association between Asp299Gly and Thr399Ile Polymorphisms in Toll-Like Receptor 4 Gene and Type 2 Diabetes Mellitus: Case-Control Study and Meta-Analysis
- *Corresponding Author:
- Daisy Crispim
Endocrine Division - Hospital de Clínicas de Porto Alegre
Rua Ramiro Barcelos 2350, Prédio 12, 4º andar
Zip Code: 90035-003, Porto Alegre-RS, Brazil
Phone: + 55 51 3359 8127
E-mail: [email protected]
Received date: May 12, 2014; Accepted date: August 25, 2014; Published date: August 30, 2014
Citation: Assmann TS, Lemos NE, de Almeida Brondani L, Carlessi R, Maldonado-Bernal C, et al. (2014) Association between Asp299Gly and Thr399Ile Polymorphisms in Toll-Like Receptor 4 Gene and Type 2 Diabetes Mellitus: Case- Control Study and Meta-Analysis. J Diabetes Metab 5:427 doi: 10.4172/2155-6156.1000427
Copyright: © 2014 Assmann TS, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Objective: This paper describes a case-control study and a meta-analysis conducted to determine whether the TLR4 Asp299Gly (rs4986790) and Thr399Ile (rs4986791) polymorphisms are associated with type 2 diabetes mellitus (T2DM).
Methods: In the case-control study were enrolled 1683 T2DM patients and 584 nondiabetic subjects from Brazil. A literature search was conducted in order to identify studies that investigated associations between the referred TLR4 polymorphisms and T2DM. Pooled odds ratios (OR) were calculated for allele contrast and dominant inheritance models.
Results: In the case-control study, genotype and allele frequencies of the Asp299Gly and Thr399Ile polymorphisms differed between T2DM patients and nondiabetic subjects (P<0.05). Moreover, the presence of the minor alleles of these polymorphisms were significantly associated with protection for T2DM, after adjusting for ethnicity, under a dominant model [Asp299Gly: OR=0.68 (95% CI 0.49-0.94); Thr399Ile: OR=0.65 (95% CI 0.46-0.90)]. Seven studies were eligible for inclusion in the meta-analysis. Meta-analysis results showed that the Asp299Gly polymorphism was associated with T2DM protection [OR=0.68 (95% CI 0.46-1.00), allele contrast model]. Stratification by ethnicity revealed that both polymorphisms were associated with T2DM protection under allele contrast and dominant models in Brazilian population but not in Europeans.
Conclusions: In our case-control study, we were able to demonstrate a possible association between the TLR4 Asp299Gly and Thr399Ile polymorphisms and protection for T2DM. In agreement, the meta-analysis results showed an association of the Asp299Gly polymorphism with T2DM protection in the whole group, and associations of the Asp299Gly and Thr399Ile polymorphisms with T2DM protection in the Brazilian group but not in European descendent. This is the largest TLR4 meta-analysis performed so far. In other ethnicities further studies with large sample size are necessary to confirm these associations in different ethnicities as well as to elucidate the roles possibly played by these polymorphisms in the pathogenesis of T2DM.