Chen Guo, Luo Lan, Zhang Miao-Miao, Wu Shou-Quan, Wang Yu, Sandford Andrew J, He Jian-Qing
Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Department of Geriatrics, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China.
Biomed Res Int. 2019 Feb 18;2019:3805405. doi: 10.1155/2019/3805405. eCollection 2019.
The Myosin Heavy Chain 15 gene () is expressed in the airway epithelium and variants in the gene have been associated with airway responsiveness. The aim of this study was to perform the first investigation of polymorphisms in relation to asthma susceptibility.
A total of 410 asthma patients and 418 controls from the Chinese Han population were enrolled in the study. Tag-single nucleotide polymorphisms were genotyped and associations between the polymorphisms and asthma risk were analyzed by logistic regression analysis adjusting for confounding factors. Dual-luciferase reporter gene analysis was performed to detect allele-dependent promoter activity of variants in HEK293 cells.
The A allele of rs9288876 decreased risk of asthma (allelic model: OR=0.808, 95% CI: 0.658-0.993, additive model: OR=0.747, 95% CI: 0.588-0.947, dominant model: OR=0.693, 95% CI: 0.502-0.955). The G alleles of both rs7635009 and rs1454197 were associated with decreased risk of asthma under the additive model (OR=0.779, 95% CI: 0.618-0.981 and OR=0.756, 95% CI: 0.600-0.953, respectively). rs9288876 allele A was associated with higher luciferase activity than allele T (<0.001). The luciferase activity of rs7635009 allele A was lower than allele G (=0.001), while rs1454197 allele T had lower luciferase activity than allele G (<0.001).
This is the first study to report the association of gene polymorphisms with asthma. Polymorphisms of rs9288876, rs7635009, and rs1454197 altered transcriptional regulation of and may be functional variants conferring susceptibility to asthma. Further study with larger sample size in different ethnic populations is needed.
肌球蛋白重链15基因()在气道上皮中表达,该基因的变异与气道反应性相关。本研究的目的是首次调查该基因多态性与哮喘易感性的关系。
本研究共纳入410例中国汉族哮喘患者和418例对照。对标签单核苷酸多态性进行基因分型,并通过调整混杂因素的逻辑回归分析来分析多态性与哮喘风险之间的关联。在HEK293细胞中进行双荧光素酶报告基因分析,以检测该基因变异的等位基因依赖性启动子活性。
rs9288876的A等位基因降低了哮喘风险(等位基因模型:OR = 0.808,95%CI:0.658 - 0.993;加性模型:OR = 0.747,95%CI:0.588 - 0.947;显性模型:OR = 0.693,95%CI:0.502 - 0.955)。在加性模型下,rs7635009和rs1454197的G等位基因均与哮喘风险降低相关(分别为OR = 0.779,95%CI:0.618 - 0.981和OR = 0.756,95%CI:0.600 - 0.953)。rs9288876的A等位基因比T等位基因具有更高的荧光素酶活性(<0.001)。rs7635009的A等位基因的荧光素酶活性低于G等位基因(=0.001),而rs1454197的T等位基因的荧光素酶活性低于G等位基因(<0.001)。
这是首次报道该基因多态性与哮喘关联的研究。rs9288876、rs7635009和rs1454197的多态性改变了该基因的转录调控,可能是赋予哮喘易感性的功能性变异。需要在不同种族人群中进行更大样本量的进一步研究。