Objective: To investigate the association between single-nucleotide polymorphisms (SNPs) in the Toll-like receptor 4 (TLR4) gene (TLR4) and the relationship between SNPs and type-2 diabetes mellitus (T2DM) complicated by tuberculosis (TB) (T2DMTB) susceptibility.
Methods: The relationship between SNPs and T2DMTB was assessed using SNPstats (<ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://bioinfo.iconcologia.net/SNPstats">http://bioinfo.iconcologia.net/SNPstats</ext-link>). Generalised multifactor dimensionality reduction (GMDR) was used to select the best interaction combination of the four SNPs. Stratified analysis was performed using logistic regression.
Results: Logistic analysis showed that both rs11536889 and rs7873784 in TLR4 were associated with risk of T2DMTB in additive and dominant models. Carriers with homozygous and heterozygous mutants of rs11536889 and rs7873784 were associated with higher T2DMTB risk than those with wild-type homozygotes (OR 1.68, 95%CI 1.22-2.17 and OR 1.61, 1.18-2.09, respectively). GMDR analysis indicated a significant two-locus model (P = 0.0107) involving rs7873784 and rs11536889; the cross-validation consistency of this model was 9/10, and testing accuracy was 60.11%. Participants with rs7873784-GC/CC and rs11536889-GC/CC genotypes had the highest risk of T2DMTB compared with participants with rs7873784-GG and rs11536889-GG genotypes (OR 3.32, 95%CI 2.12-4.63).
Conclusions: We found that> rs11536889 and rs7873784 in the TLR4 gene, and their interactions, were associated with increased T2DMTB risk.