Effects of Lung Function-Related Genes and TSLP on COPD Phenotypes
Effects of Lung Function-Related Genes and TSLP on COPD Phenotypes
复制标题
肺功能相关基因和 TSLP 对 COPD 表型的影响
DOI：
10.1080/15412555.2019.1708296
复制
发表时间：
2020
期刊：
影响因子：
2.2
通讯作者：
Hizawa N
中科院分区：
文献类型：
--
作者：
Yamada H;Hida N;Masuko H;Sakamoto T;Hizawa N
基于16个SNP的加权遗传风险评分(GRS)在日本和非日本人群中都与肺功能降低有关，以前曾与COPD和哮喘的发病有关。我们在这里研究了这种肺功能GRS对特定COPD表型的遗传影响。一组日本COPD患者(N= 270)接受了肺功能测试，然后用16个SNP和TSLP上的表达数量性状基因座(rs2289276，rs3806933)进行了等位基因特异性阵列的基因分型。肺功能GRS评分和两步聚类分析根据性别、年龄、吸烟指数、%FEV1和肺功能GRS将COPD患者分为不同的表型。TSLP对COPD表型的遗传效应与肺功能GRS的交互作用也被检测。共有270名参与者被分成5个组。肺功能GRS水平最高的集群的特征是中度到严重的气流阻塞和最高的血嗜酸性粒细胞计数。根据TSLP，在以中到重度气流阻塞和重度吸烟为特征的人群中，T等位基因数量增加(rs2289276，p值=0.035；rs3806933，p值=0.047)，而不受肺功能GRS的影响。肺功能受损的遗传易感性增加了患COPD的风险，其特征是嗜酸性粒细胞计数增加和严重的气流阻塞，而对外部刺激反应增强的TSLP个体在大量吸烟的情况下发生严重气流阻塞的独立风险。
A weighted genetic risk score (GRS) based on 16 SNPs implicated in reduced lung function in both Japanese and non-Japanese populations was previously associated with the onset of COPD and asthma. We here examine the genetic impact of this lung function GRS on specific COPD phenotypes. A cohort of Japanese COPD patients (N= 270) underwent lung function testing followed by genotyping with allele-specific arrays for 16 SNPs as well as expression quantitative trait loci atTSLP(rs2289276, rs3806933). Lung function GRS scoring and two-step cluster analyses grouped patients into different COPD phenotypes based on gender, age, smoking index, %FEV1and lung function GRS. The genetic effect ofTSLPon COPD phenotypes was also examined for interactions with the lung function GRS. A total of 270 participants were grouped into 5 clusters. The cluster with the highest levels of lung function GRS was characterized by moderate to severe airflow obstruction and the highest blood eosinophil counts. RegardingTSLP, an increased number of T alleles at both SNPs was found in the cluster characterized by moderate to severe airflow obstruction and heavy smoking (rs2289276,pvalue = 0.035; rs3806933,pvalue = 0.047) independent of the lung function GRS. A genetic susceptibility to impaired lung function carries an increased risk of developing COPD characterized by increased eosinophil counts and severe airflow obstruction while individuals with increasedTSLPresponses to external stimuli have an independent risk of developing severe airflow obstruction in the presence of heavy smoking.