Polymorphisms in the FCER2 gene have associations with asthma and chronic obstructive pulmonary disease.
Polymorphisms in the FCER2 gene have associations with asthma and chronic obstructive pulmonary disease.
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DOI：
10.21037/jtd-22-820
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发表时间：
2023-02-28
影响因子：
2.5
通讯作者：
中科院分区：
文献类型：
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作者：
哮喘和慢性阻塞性肺疾病（COPD）是异源性疾病，有许多相似之处。荷兰假说提出，这两种疾病可能有共同的遗传起源。本研究旨在探讨哮喘和COPD在中国患者中是否具有共同的遗传背景。在本病例对照研究中，使用SNaPshot对单核苷酸多态性（snp）进行基因分型。应用单倍型疾病分析和单倍型表型分析评估FCER2基因三种多态性与COPD/哮喘风险的关系。此外，分析了FCER2基因多态性与表型之间的关系。我们检测到7个基因（FCER1A、FCGR2A、FCGR2B、CHI3L1、ADRB2、STAT6和FCER2）在气道上皮细胞中表达的10个snp。我们检测了251名COPD患者、597名哮喘患者和632名健康对照者的基因型和等位基因分布。COPD患者与对照组FCER2基因（rs28364072）存在显著差异（P=0.009）。哮喘患者与对照组rs1801274 （FCGR2A）、rs12368672 （STAT6）、rs2228137 （FCER2）基因型及等位基因分布差异有统计学意义（P分别为0.004、0.007、0.010）。值得注意的是，FCER2基因多态性与COPD （rs28364072的P=0.009）和哮喘（rs2228137的P=0.01）的风险相关。单倍型分析显示，单倍型T-G-T（分别为rs28364072、rs2228137和rs3760687等位基因）与哮喘的高发病风险显著相关[比值比(OR) =2.25, 95%可信区间（CI）： 1.26-4.01， P=0.006]。进一步分析表明，C-A-C单倍型和C-G-T单倍型与COPD或哮喘患者血嗜酸性粒细胞增加相关（P=0.034， P<0.001）。单倍型C-A-C、C-G-C和T-G-C与哮喘患者血清IgE水平有显著相关性（P分别为0.002、0.041和0.004）。我们的数据表明，FCER2基因可能与哮喘和COPD的易感性相关，而FCER2单倍型与两种疾病的肺功能测量和血嗜酸性粒细胞计数相关。我们的研究结果支持哮喘和COPD的共同遗传基础，提示这两种疾病的潜在治疗靶点。
Asthma and chronic obstructive pulmonary disease (COPD) are heterogenetic diseases and exhibit many similarities. Dutch hypothesis proposed that these two diseases may have common genetic origins. This study aims to investigate whether asthma and COPD share a common genetic background in Chinese patients. In this case-control study, single nucleotide polymorphisms (SNPs) were genotyped using SNaPshot. Haplotype disease analysis and haplotype phenotype analysis were applied to assess the relationship between three polymorphisms of the FCER2 gene and the risk of COPD/asthma. Additionally, associations between polymorphisms of the FCER2 gene and phenotypes were analyzed. We detected ten SNPs of seven genes (FCER1A, FCGR2A, FCGR2B, CHI3L1, ADRB2, STAT6, and FCER2) expressed by airway epithelial cells. We detected genotypes and allele distributions in 251 COPD patients, 597 asthma patients, and 632 healthy controls. A significant difference was found in the FCER2 gene (rs28364072) between COPD patients and controls (P=0.009). Significant differences were observed in the genotype and allele distributions of rs1801274 (FCGR2A), rs12368672 (STAT6), and rs2228137 (FCER2) between asthma patients and controls (P=0.004, 0.007 and 0.010, respectively). Notably, polymorphisms of FCER2 gene were associated with the risk of both COPD (P=0.009 for rs28364072) and asthma (P=0.01 for rs2228137). Haplotype analysis revealed that haplotype T-G-T (alleles of rs28364072, rs2228137, and rs3760687, respectively) was significantly associated with a higher risk of asthma [odds ratios (OR) =2.25, 95% confidence interval (CI): 1.26–4.01, P=0.006]. Further analysis showed that the C-A-C haplotype and C-G-T haplotype were associated with increased blood eosinophils in either COPD or asthma patients (P=0.034, and P<0.001, respectively). Moreover, haplotypes C-A-C, C-G-C, and T-G-C showed significant associations with serum IgE levels in asthma patients (P=0.002, 0.041, and 0.004, respectively). Our data suggest that the FCER2 gene might associate with predisposition to asthma and COPD, while FCER2 haplotypes were associated with pulmonary function measurements and blood eosinophils counts in both diseases. Our findings support the common genetic basis for asthma and COPD, suggesting a potential therapeutic target for the two diseases.
DOI：
10.1183/09031936.00001914
发表时间：
2014-10
期刊：
The European respiratory journal
影响因子：
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作者：
Smolonska J;Koppelman GH;Wijmenga C;Vonk JM;Zanen P;Bruinenberg M;Curjuric I;Imboden M;Thun GA;Franke L;Probst-Hensch NM;Nürnberg P;Riemersma RA;van Schayck CP;Loth DW;Brusselle GG;Stricker BH;Hofman A;Uitterlinden AG;Lahousse L;London SJ;Loehr LR;Manichaikul A;Barr RG;Donohue KM;Rich SS;Pare P;Bossé Y;Hao K;van den Berge M;Groen HJ;Lammers JW;Mali W;Boezen HM;Postma DS
通讯作者：
Postma DS