Abstract
Previous studies have demonstrated that integrins are involved in the aetiology of asthma. Several single-nucleotide polymorphisms (SNPs) in the integrin β3 (ITGB3) gene are significantly associated with asthma in Western populations. Given the important roles of environmental exposures in the development of asthma, we evaluated the associations between six SNPs in ITGB3 and asthma in Chinese Han children. A total of 321 unrelated Chinese children with asthma and 315 healthy children were recruited for the study. SNP genotyping was performed by high-resolution melting analysis (HRM). The selected SNPs were well genotyped by HRM, and SNP rs3809865 in the 3′ untranslated region (3′UTR) of ITGB3 was found to be strongly associated with asthma (adjusted p = 0.004). The minor allele of rs3809865 showed a protective effect against asthma (OR: 0.59; 95% CI: 0.43–0.8). The seed regions of two miRNAs (hsa-mir-124 and hsa-mir-506) were predicted to bind to the sequence containing rs3809865 by TargetScan and PITA. Luciferase reporter assays demonstrated that the T allele of rs3809865 was more efficiently targeted by hsa-mir-124 than was the A allele, which suggested that rs3809865 could affect the binding of hsa-mir-124 to ITGB3. Furthermore, the transfection of A549 cells with hsa-mir-124 resulted in the downregulation of ITGB3 expression. Our results revealed that rs3809865 was significantly associated with asthma due to its effect on the binding of hsa-mir-124 to ITGB3.
Highlights
Asthma is one of the most common chronic diseases in children, and it is characterised by bronchial hyperresponsiveness (BHR) and reversible airway obstruction
Five single nucleotide polymorphisms (SNPs) in the Integrin b3 (ITGB3) gene have been linked with asthma in a Hutterite population, but these results were not observed in three other unrelated populations, most likely due to differences in environmental exposures in childhood [2]
The genotyping was especially successful for rs3809865 with the similar GC content, which suggested that small amplicons were good substrates for SNP genotyping by the high-resolution melting analysis (HRM) method
Summary
Asthma is one of the most common chronic diseases in children, and it is characterised by bronchial hyperresponsiveness (BHR) and reversible airway obstruction. Both genetic and environmental factors play important roles in the development of asthma. Rogers et al demonstrated that few identified SNPs could be replicated in different populations [3]. Factors such as the criteria used to diagnose asthma, environmental exposures, numbers of subjects, different patterns of linkage disequilibrium, and population stratification could be potential causes of this non-repeatability [3,4]. It is necessary to identify single nucleotide polymorphisms (SNPs) in the ITGB3 gene associated with asthma in a Chinese population
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