We identified HLA-G as an asthma susceptibility gene in multiple populations and demonstrated that variation in this gene influences subsequent risk for asthma.
In this study, we present evidence from four independent samples in support of HLA-G as a novel asthma and bronchial hyperresponsiveness susceptibility gene in the human leukocyte antigen region on chromosome 6p21, and we speculate that this gene might contribute to risk for other inflammatory diseases that show linkage to this region.
Here we report a SNP in the 3' untranslated region of HLA-G that influences the targeting of three microRNAs (miRNAs) to this gene, and we suggest that allele-specific targeting of these miRNAs accounts, at least in part, for our earlier observations on HLA-G and the risk of asthma.
Here we report a SNP in the 3' untranslated region of HLA-G that influences the targeting of three microRNAs (miRNAs) to this gene, and we suggest that allele-specific targeting of these miRNAs accounts, at least in part, for our earlier observations on HLA-G and the risk of asthma.
We found that DPP10 was significantly associated with bronchial hyperresponsiveness (BHR) and BHR asthma after the adjustment for multiple testing; while the associations of PHF11 with positive skin reactions to antigens and the associations of HLA-G with BHR asthma were only nominally significant.
These combined results are consistent with +3142 allele-specific targeting of HLA-G by the miR-152 family and support our hypothesis that miRNA regulation of sHLA-G in the airway is influenced by both the asthma status of the subject's mother and the subject's genotype.
As the NK cell receptor KIR2DL4 has been reported to induce interferon gamma (IFNγ) secretion when ligated with HLA-G, we postulated that the 9A/10A genetic polymorphism of KIR2DL4 which influences receptor structure may influence susceptibility to asthma.
These microRNAs suppress HLA-G expression, and rs1063320, a common SNP in the HLA-G 3'UTR that is associated with asthma risk, modulates miRNA binding.
Individual variation in HLA-G expression is linked to its genetic polymorphism and has been associated with many pathological situations such as asthma, which is characterized by epithelium abnormalities and inflammatory cell activation.