Genetic Variation of ITGB3 Is Associated with Asthma in Chinese Han Children

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.

Small RNA profiling reveals deregulated phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/Akt pathway in bronchial smooth muscle cells from asthmatic patients

“…49 Considering other targets of the asthma-deregulated miRNome, ITGB3 has been suggested as a potential therapeutic target for the treatment of asthma because of its role in the pathogenesis of the disease and sensitization to mold allergens 50,51 and the fact that several single nucleotide polymorphisms in this gene are associated with asthma. [52][53][54] Considering BMPR2, altered expression of this gene was shown to inhibit proliferation of vascular smooth muscle with resultant pulmonary hypertension, [55][56][57] whereas PHB was suggested to be responsible for reducing allergic airway inflammation. 58 Finally, PTEN has been linked to chronic obstructive pulmonary disease and can regulate cell-cycle progression and cellular survival through the AKT signaling pathway.…”

Association of CD14 C159T polymorphism with atopic asthma susceptibility in children from Southeastern China: a case-control study

“…All patients were recruited from the Affiliated Children's Hospital, Soochow University. The diagnosis of asthma in all subjects was performed by asthma specialists according to previously described criteria (Zhang et al, 2013). The 362 children with asthma ranged from 2-12 years of age and included 199 males and 163 females.…”

Identification ofITGA2BandITGB3Single-Nucleotide Polymorphisms and Their Influences on the Platelet Function

“…However, limited information was available on other genetic polymorphisms of ITGA2B and ITGB3 in Asian populations or their association with the platelet function [11, 12]. Moreover, the prevalence of the PlA2 allele (rs5918) is dependent on ethnicity, with a frequency of approximately 15/100 in Caucasian populations [13] falling to less than 1/100 in Oriental populations [12, 14]. …”