Department of Pulmonary Medicine, University of Tsukuba, Tsukuba, Japan.
Department of Pulmonary Medicine, University of Tsukuba, Tsukuba, Japan.
Allergol Int. 2017 Oct;66(4):563-567. doi: 10.1016/j.alit.2017.02.012. Epub 2017 Mar 17.
Recent studies have demonstrated that a coding SNP (rs6967330, Cys529→Tyr) in cadherin-related family member 3 (CDHR3), which was previously associated with wheezing illness and hospitalizations in infancy, could support efficient human rhinovirus C (RV-C) entry and replication. Here, we sought to examine the genetic contribution of this variant to the development of adult asthma.
We performed a candidate gene case-control association study of 2 independent Japanese populations (a total of 3366 adults). The odds ratios (ORs) for association of the A allele at rs6967330 with adult asthma were calculated according to age at onset of asthma. In addition, the effect of the CDHR3 genotype on the development of specific asthma phenotypes was examined.
The A allele was associated with asthma (OR = 1.56; Mantel-Haenszel p = 0.0040) when the analysis was limited to patients with early-onset adult asthma. In addition, when the analysis was limited to atopic individuals, a stronger association of the CDHR3 variant with early-onset asthma was found, and interaction of the CDHR3 genotype with atopy was demonstrated. Finally, a significant association of this variant was specifically found with a phenotype of asthma characterized by atopy, early-onset, and lower lung function.
Our study supports the concept that the CDHR3 variant is an important susceptibility factor for severe adult asthma in individuals who develop the disease in early life. The interaction between the CDHR3 variant and atopy indicates that genetic predisposition to early respiratory viral infection is combined with atopy in promoting asthma.
最近的研究表明，钙黏蛋白相关家族成员 3（CDHR3）中的一个编码单核苷酸多态性（rs6967330，Cys529→Tyr），之前与婴儿期的喘息病和住院有关，可能支持人类鼻病毒 C（RV-C）的有效进入和复制。在这里，我们试图研究该变体对成人哮喘发展的遗传贡献。
我们对两个独立的日本人群（共 3366 名成年人）进行了候选基因病例对照关联研究。根据哮喘发病年龄计算 rs6967330 处 A 等位基因与成人哮喘关联的优势比（OR）。此外，还检查了 CDHR3 基因型对特定哮喘表型发展的影响。
当分析仅限于早发性成人哮喘患者时，A 等位基因与哮喘相关（OR=1.56；Mantel-Haenszel p=0.0040）。此外，当分析仅限于特应性个体时，发现 CDHR3 变体与早发性哮喘的关联更强，并且证实了 CDHR3 基因型与特应性的相互作用。最后，发现该变体与特应性、早发性和较低肺功能为特征的哮喘表型存在显著关联。
我们的研究支持这样一种概念，即 CDHR3 变体是个体在生命早期发生疾病时发生严重成人哮喘的重要易感因素。CDHR3 变体与特应性的相互作用表明，早期呼吸道病毒感染的遗传易感性与特应性相结合，促进了哮喘的发生。
