Journal
GENETIC EPIDEMIOLOGY
Volume 26, Issue 2, Pages 155-165Publisher
WILEY
DOI: 10.1002/gepi.10298
Keywords
interleukin 10 (IL10); single nucleotide polymorphism (SNP); genetic association; family-based association test (FBAT); haplotype; promoter; 3 '; untranslated region (3 ' UTR)
Funding
- NHLBI NIH HHS [U01 HL 66795, R01 HL66386, N01-HR-16048, N01-HR-16047, N01HR16044, N01-HR-16044, T32 HL007427, U01 HL066795, N01-HR-16050, T32HL07427, N01-HR-16052, N01-HR-16046, N01-HR-16049, N01-HR-16045, N01-HR-16051, K23 HL004278] Funding Source: Medline
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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 FEV1 as a percent of predicted (FEV1PP) (P=0.0002) in both the family and population analyses. The promoter haplotype GCC was positively associated with IgE levels and FEV1PP (P=0.007 and 0.012, respectively). The promoter haplotype ATA was negatively associated with InPC20 and FEV1PP (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.
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