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


CONCLUSIONS
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.
Munthe-Kaas
Monica Cheng
MC
Department of Pediatrics, Oslo University Hospital, Oslo, Norway. m.c.munthe-kaas@medisin.uio.no
Torjussen
Tale Maehre
TM
Gervin
Kristina
K
Lødrup Carlsen
Karin C
KC
Carlsen
Kai Håkon
KH
Granum
Berit
B
Hjorthaug
Hanne Sagsveen
HS
Undlien
Dag
D
Lyle
Robert
R
D001249:Asthma / Q000097:blood / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000097:blood*; D019175:DNA Methylation; D005260:Female; D005312:Fetal Blood; D005500:Follow-Up Studies; D018507:Gene Expression Regulation, Developmental; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D013997:Time Factors
D018950:Lipopolysaccharide Receptors; D004247:DNA