Dahl Morten, Tybjaerg-Hansen Anne, Lange Peter, Nordestgaard Børge G
Department of Clinical Biochemistry, Herlev University Hospital, DK-2730 Herlev, Denmark.
Respir Res. 2005 Oct 9;6(1):113. doi: 10.1186/1465-9921-6-113.
Carriers of cystic fibrosis intron-8 5T alleles with high exon-9 skipping could have increased annual lung function decline and increased risk for asthma or chronic obstructive pulmonary disease (COPD).
We genotyped 9131 individuals from the adult Danish population for cystic fibrosis 5T, 7T, 9T, and F508del alleles, and examined associations between 11 different genotype combinations, and annual FEV1 decline and risk of asthma or COPD.
5T heterozygotes vs. 7T homozygous controls had no increase in annual FEV1 decline, self-reported asthma, spirometry-defined COPD, or incidence of hospitalization from asthma or COPD. In 5T/7T heterozygotes vs. 7T homozygous controls we had 90% power to detect an increase in FEV1 decline of 8 ml, an odds ratio for self-reported asthma and spirometry-defined COPD of 1.9 and 1.7, and a hazard ratio for asthma and COPD hospitalization of 1.8 and 1.6, respectively. Both 5T homozygotes identified in the study showed evidence of asthma, while none of four 5T/F508del compound heterozygotes had severe pulmonary disease. 7T/9T individuals had annual decline in FEV1 of 19 ml compared with 21 ml in 7T homozygous controls (t-test: P = 0.03). 6.7% of 7T homozygotes without an F508del allele in the cystic fibrosis transmembrane conductance regulator gene reported asthma vs. 11% of 7T/9T individuals with an F508del allele (chi2: P = 0.01) and 40% of 7T homozygotes with an F508del allele (P = 0.04). 7T homozygotes with vs. without an F508del allele also had higher incidence of asthma hospitalization (log-rank: P = 0.003); unadjusted and adjusted equivalent hazard ratios for asthma hospitalization were 11 (95%CI: 1.5-78) and 6.3 (0.84-47) in 7T homozygotes with vs. without an F508del allele.
Polythymidine 5T heterozygosity is not associated with pulmonary dysfunction or disease in the adult Caucasian population. Furthermore, our results support that F508del heterozygosity is associated with increased asthma risk independently of the 5T allele.
携带囊性纤维化内含子8 5T等位基因且外显子9跳跃率高的个体，其每年肺功能下降可能加剧，患哮喘或慢性阻塞性肺疾病（COPD）的风险也可能增加。
我们对来自丹麦成年人群的9131名个体进行了囊性纤维化5T、7T、9T和F508del等位基因的基因分型，并研究了11种不同基因型组合与每年第一秒用力呼气容积（FEV1）下降以及哮喘或COPD风险之间的关联。
与7T纯合子对照组相比，5T杂合子的FEV1年下降率、自我报告的哮喘、肺功能测定定义的COPD或因哮喘或COPD住院的发生率均未增加。在5T/7T杂合子与7T纯合子对照组中，我们有90%的把握度检测到FEV1下降增加8毫升，自我报告的哮喘和肺功能测定定义的COPD的优势比分别为1.9和1.7，哮喘和COPD住院的风险比分别为1.8和1.6。研究中鉴定出的两名5T纯合子均有哮喘证据，而四名5T/F508del复合杂合子均无严重肺部疾病。7T/9T个体的FEV1年下降量为19毫升，而7T纯合子对照组为21毫升（t检验：P = 0.03）。在囊性纤维化跨膜传导调节基因中无F508del等位基因的7T纯合子中，6.7%报告有哮喘，而在有F508del等位基因的7T/9T个体中这一比例为11%（卡方检验：P = 0.01），在有F508del等位基因的7T纯合子中为40%（P = 0.04）。有与无F508del等位基因的7T纯合子的哮喘住院发生率也更高（对数秩检验：P = 0.003）；有与无F508del等位基因的7T纯合子哮喘住院的未调整和调整后的等效风险比分别为11（95%置信区间：1.5 - 78）和6.3（0.84 - 47）。
在成年白种人群中，多聚胸腺嘧啶5T杂合性与肺功能障碍或疾病无关。此外，我们的结果支持F508del杂合性与哮喘风险增加相关，且独立于5T等位基因。
Zotero 插件