IL10 gene polymorphisms are associated with asthma phenotypes in children.
IL10 is an anti-inflammatory cytokine that has been found to have lower production in macrophages and mononuclear cells from asthmatics. Since reduced IL10 levels may influence the severity of asthma phenotypes, we examined IL10 single-nucleotide polymorphisms (SNPs) for association with asthma severity and allergy phenotypes as quantitative traits. Utilizing DNA samples from 518 Caucasian asthmatic children from the Childhood Asthma Management Program (CAMP) and their parents, we genotyped six IL10 SNPs: 3 in the promoter, 2 in introns, and one in the 3' UTR. Using family-based association tests, each SNP was tested for association with asthma and allergy phenotypes individually. Population-based association analysis was performed with each SNP locus, the promoter haplotypes and the 6-loci haplotypes. The 3' UTR SNP was significantly associated with FEV(1) as a percent of predicted (FEV(1)PP) (P=0.0002) in both the family and population analyses. The promoter haplotype GCC was positively associated with IgE levels and FEV(1)PP (P=0.007 and 0.012, respectively). The promoter haplotype ATA was negatively associated with lnPC(20) and FEV(1)PP (P=0.008 and 0.043, respectively). Polymorphisms in IL10 are associated with asthma phenotypes in this cohort. Further studies of variation in the IL10 gene may help elucidate the mechanism of asthma development in children.
Lyon
Helen
H
Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Lange
Christoph
C
Lake
Stephen
S
Silverman
Edwin K
EK
Randolph
Adrienne G
AG
Kwiatkowski
David
D
Raby
Benjamin A
BA
Lazarus
Ross
R
Weiland
Katy M
KM
Laird
Nan
N
Weiss
Scott T
ST
D020413:3' Untranslated Regions / Q000235:genetics; D001249:Asthma / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D002874:Chromosome Mapping / Q000706:statistics & numerical data; D002878:Chromosomes, Human, Pair 1; D015331:Cohort Studies; D005260:Female; D005541:Forced Expiratory Volume / Q000235:genetics; D005820:Genetic Testing / Q000706:statistics & numerical data; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D007438:Introns / Q000235:genetics; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008957:Models, Genetic; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012130:Respiratory Hypersensitivity / Q000453:epidemiology / Q000235:genetics
D020413:3' Untranslated Regions; D016753:Interleukin-10