CD14, Endotoxin, and Asthma Risk: Actions and Interactions

Abstract

A functional single nucleotide polymorphism in the 5 genomic region of CD14 (CD14/Ϫ159) is one of the most widely tested genetic variations in relation to asthma and associated traits. The results of these studies have shown a remarkable, statistically significant heterogeneity, with some studies indicating the T-allele as a risk factor, others the C-allele, and others finding no association. Recent studies in which exposure to house-dust endotoxin or to domestic sources of microbial exposure were assessed concomitantly with CD14/Ϫ159 have shown a consistent, replicable gene-environment interaction. Specifically, results suggest that the C-allele is a risk factor for allergic phenotypes at low levels of exposure, whereas the T-allele is a risk factor at high levels of exposure. This finding seems to be explained by a genetically-determined heterogeneity for the protective effect of microbial exposure on allergic phenotypes, with homozygotes for the C-allele showing a much stronger negative association between exposure and allergic outcomes than carries of the other two genotypes. These results suggest that the often encountered, limited replicability of genetic associations may, at least in part, be due to complex interactions between genes and environment in determining asthma-related outcomes.

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

“…26 However, the present study is the first to our knowledge that investigates possible association between CD14 and T1D. Although we cannot exclude a small effect of the tested polymorphisms in these two genes on development of T1D or allergic asthma, they do not seem to play any major role in the pathogenesis of these phenotypes in our populations.…”

Therapeutic Targeting of Toll-Like Receptors for Infectious and Inflammatory Diseases and Cancer

“…A SNP in the 5Ј genomic region of CD14 at position Ϫ159 (Martinez, 2007) is associated with infectious diseases, asthma, and allergy (Wiertsema et al, 2006). A number of other diseases have also been linked to this polymorphism, from cardiovascular disease to autoimmunity and from infections to malignancies (Martinez, 2007).…”

Protective effects of farming on allergies and asthma: have we learnt anything since 1873?

“…In farmers' children, a bimodal effect of CD14/-260 on atopy was shown, with the direction of the effect being dependent on the type and level of environmental exposures (i.e., pets, livestock and endotoxin) [64]. Indeed, it has been suggested that either genotype has the capacity to be beneficial or detrimental in terms of atopy risk, depending upon the nature of the exposure [67]. Another polymorphism in the NOD1/CARD4 gene, which encodes an alternative intracellular receptor involved in the innate recognition of microbial components, shows a similar protective effect against allergy for T homozygosity [68].…”