Literature DB >> 20398919

CD14 polymorphisms and serum CD14 levels through childhood: a role for gene methylation?

Monica Cheng Munthe-Kaas1, Tale Maehre Torjussen, Kristina Gervin, Karin C Lødrup Carlsen, Kai Håkon Carlsen, Berit Granum, Hanne Sagsveen Hjorthaug, Dag Undlien, Robert Lyle.   

Abstract

BACKGROUND: CD14 is a pattern-recognition receptor for environmental LPS, and engagement of the CD14-LPS complex activates innate host defense mechanisms. Single nucleotide polymorphisms (SNPs) in the CD14 gene have been associated with soluble CD14 (sCD14) levels, but inconsistencies between studies suggest the presence of regulatory mechanisms hitherto not well understood.
OBJECTIVE: We sought to investigate possible associations between CD14 SNPs and sCD14 levels at different time points in childhood (at birth [cord blood] and 2 and 10 years) and to explore whether these associations were related to CD14 gene methylation.
METHODS: Four SNPs, rs2569191 (-1145GA), rs5744455 (-550CT or -651CT), rs2569190 (-159CT or -260CT), and rs4914 in CD14 were genotyped in 762 children from the Environmental and Childhood Asthma study. Genotype frequencies were analyzed for association with sCD14 levels in 660 babies, 346 children at age 2 years, and 360 children at age 10 years. In a subgroup of 157 children with DNA available at both 2 and 10 years of age, CD14 methylation patterns were determined and analyzed against detected CD14 gene-sCD14 associations.
RESULTS: rs2569191, rs5744455, and rs2569190 were associated with sCD14 levels at birth and 2 years, but only rs5744455 was associated with sCD14 levels at 10 years. CD14 methylation increased significantly from age 2 to 10 years, and the level of methylation was inversely correlated with sCD14 levels at 10 years.
CONCLUSION: The reduced effect of CD14 polymorphisms on sCD14 levels from early to late childhood paralleled a small but significant increase in CD14 methylation during the same period. Copyright (c) 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

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Year:  2010        PMID: 20398919     DOI: 10.1016/j.jaci.2010.02.010

Source DB:  PubMed          Journal:  J Allergy Clin Immunol        ISSN: 0091-6749            Impact factor:   10.793


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