These data indicate that only the combined analyses of genetic alterations in the IL-4/IL-13 pathway reveal its actual significance to the development of atopy and childhood asthma.
Orosomucoid like 3 (ORMDL3), a gene localized to chromosome 17q21, has been linked in epidemiologic studies to childhood asthma and rhinovirus (RV) infections.
Genome-wide association studies have established a strong correlation between elevated expression of the endoplasmic reticulum protein ORMDL3 and risk for childhood asthma.
Polymorphisms in a putative promoter region of ORMDL3, which are associated with childhood asthma, alter transcriptional regulation of ORMDL3, correlate with changes in TH2 cytokines levels, and therefore might contribute to the childhood asthma susceptibility signal from 17q21.
The 6 loci (IL-13C-1112T, IL-13C1923T, IL-4 C-590T, IL-4RA 175V, FcER1B E237G and 12-ADR Q27E) make little contribution to the development of asthma in children of Chinese Han nationality.
Only recently a new asthma susceptibility gene (ORMDL3) has been identified by a whole genome association study, considered to be a major determinant for childhood asthma.
Here we reveal the function in sphingolipid metabolism of the ORM genes (known as ORMDL genes in humans)-a conserved gene family that includes ORMDL3, which has recently been identified as a potential risk factor for childhood asthma.
We examined whether polymorphisms in ORMDL3 and the adjacent gasdermin-like (GSDML) gene associated with asthma in the genome-wide association study are related to childhood asthma and atopy in a Mexico City population.
Recent genome-wide association studies linked childhood asthma with single-nucleotide polymorphisms (SNPs) in ORM1-like protein 3 (ORMDL3) gene region on chromosome 17q21.
However, IFN-γ/IL-13 and IFN-γ/IL-4 ratios during pregnancy were associated with a decreased risk of childhood asthma (n = 381; odds ratio [OR], 0.33; 95% confidence interval [CI], 0.17-0.66; P = 0.002; and n = 368; OR, 0.36; 95% CI, 0.18-0.71; P = 0.003, respectively).
The gene polymorphisms of Arg130Gln in IL-13 and -590C/T in IL-4 gene promoter region were analyzed using the polymerase chain reaction (PCR) and direct gene sequencing; the asthma-related indexes were detected using the enzyme-linked immunosorbent assay, and the relevant indexes were analyzed; moreover, whether there was a synergistic effect between Arg130Gln in IL-13 and -590C/T in IL-4 gene promoter region in the pathogenesis of asthma in children was analyzed.
In a genome-wide association study, genetic variants on chromosome 17q21 were strongly associated with childhood asthma and orosomucoid 1-like 3 (ORMDL3) gene expression.
The SNP rs7216389, which tags the 3' flanking region of ORMDL3 at 17q21 and has been associated with childhood asthma, was correlated with increased glioma risk (OR = 1.10; 95% CI: 1.01-1.19).
We conclude that the ORMDL3 gene influences childhood asthma and that the TT genotype of the rs7216389 polymorphism is associated with childhood asthma in the Chinese population.