No Association of TLR2 and TLR4 Polymorphisms with Type I Diabetes Mellitus in the Basque Population

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Abstract
The destruction of pancreatic beta cells that occurs in type 1 diabetes mellitus (T1DM) is mediated by the immune system, and evidence has accumulated supporting the implication of innate immune mediators. Toll-like receptors (TLRs) participate in the first line of immune defense through antigen recognition, and their ligands are mostly exogenous but can be host-derived as well. To test the possible role of TLRs in the development of T1DM, we studied different SNPs of TLR2 (N199N, S450S, R677W, and R753Q) and TLR4 (D299G, T399I, and S400N) in Basque families with T1DM. Several positions analyzed were not polymorphic in the Basque population. Genetic association analysis failed to demonstrate any association of these polymorphisms of TLR2 and TLR4 with T1DM in our population. The differences in TLR4 haplotype transmission to affected and unaffected offspring are indicative of a possible implication of TLR4 in disease risk but differences did not reach statistical significance.