A TLR2 polymorphism is associated with type 1 diabetes and allergic asthma

Abstract

Type 1 diabetes (T1D) and allergic asthma are immune-mediated diseases. Pattern recognition receptors are proteins expressed by cells in the immune system to identify microbial pathogens and endogenous ligands. Toll-like receptors (TLRs) and CD14 are members of this family and could represent a molecular link between microbial infections and immune-mediated diseases. Diverging hypotheses regarding whether there exists a common or inverse genetic etiology behind these immunemediated diseases have been presented. We aimed to test whether there exist common or inverse associations between polymorphisms in the pattern recognition receptors TLR2, TLR4 and CD14 and T1D and allergic asthma. Eighteen single nucleotide polymorphisms (SNPs) were genotyped in TLR2 (2), TLR4 (12) and CD14 (4) in 700 T1D children, 357 nuclear families with T1D children and 796 children from the 'Environment and Childhood Asthma' study. Allele and haplotype frequencies were analyzed in relation to diseases and in addition transmission disequilibrium test analyses were performed in the family material. Both T1D and allergic asthma were significantly associated with the TLR2 rs3804100 T allele and further associated with the haplotype including this SNP, possibly representing a susceptibility locus common for the two diseases. Neither TLR4 nor CD14 were associated with T1D or allergic asthma.

Significant Association between Toll-Like Receptor Gene Polymorphisms and Posttransplantation Diabetes Mellitus

“…Gene polymorphisms in TLRs affect the innate immune response [25]. Previous studies have recognized that polymorphisms in TLRs are associated with the development of diabetes [14,26,27,28,29,30,31,32,33,34,35,36]. Table 5 shows polymorphisms previously associated with diabetes and references.…”

“…Table 5 shows polymorphisms previously associated with diabetes and references. Bjørnvold et al [28] reported that the TLR2 rs3804100 SNP is associated with T1DM. However, our data did not show a significant association between TLR2 SNPs and PTDM.…”

Genetics and epidemiology: asthma and infection

“…Polymorphisms of TLR1, TLR6 and TLR10 (these receptors can form heterodimers with TLR2) were reported to exert a protective effect against asthma [27]. Several studies have identified significant associations between TLR2 polymorphisms and increased risk of asthma [27,28,34], whereas polymorphisms of TLR3 were not associated with asthma [27]. Infectious agents potentially interact with other environmental factors such as family size, country versus city living, attendance at day care centres, schools and so on to influence the development of asthma.…”

ORMDL3 variants associated with bronchiolitis susceptibility in a Chinese population

“…The common genetic risks for bronchiolitis and asthma have recently been reviewed (Bartlett et al, 2009). These genes include those involved in the innate/Th1 response to infection [e.g., Toll-like receptors and CD14 (Hong et al, 2007;Kormann et al, 2008;Bjornvold et al, 2009)], and those encoding for interferons [e.g., interferon-γ gene (Kumar and Ghosh, 2008), interferon regulatory factor-1 gene (Schedel et al, 2008)], as well as the interleukin-13 and interleukin-14 genes (Forton et al, 2009). The sequence variant rs7216389 in ORMDL3 was shown to be associated with the risk of childhood asthma in a genome-wide association study of asthma (Moffatt et al, 2007).…”