Background 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. Methods 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. Results 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. Conclusions 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.
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机译：背景技术最近的研究表明，钙粘蛋白相关家族成员3（CDHR3）中的编码SNP（rs6967330，Cys529→Tyr）以前与喘息性疾病和婴儿期住院有关，可以支持有效的人类鼻病毒C（RV-C）输入和复制。在这里，我们试图检查这种变异对成人哮喘发展的遗传贡献。方法我们对2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研究。根据哮喘发作的年龄，计算rs6967330处的A等位基因与成人哮喘的比值比（OR）。此外，检查了CDHR3基因型对特定哮喘表型发展的影响。结果当分析仅限于早期发作的成年哮喘患者时，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变异与早期发作的哮喘之间存在更强的关联，并且证明了CDHR3基因型与特应性的相互作用。最后，该变体与特征在于特应性，早发病和肺功能低下的哮喘表型之间特别相关。结论我们的研究支持CDHR3变异体是严重的成年哮喘患者的重要易感因素这一观念，这种个体在生命早期发展为该疾病。 CDHR3变异体与特应性之间的相互作用表明，早期呼吸道病毒感染的遗传易感性与特应性相结合促进哮喘。
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