A Disintegrin and Metalloprotease 33 polymorphisms and lung function decline in the general population
A Disintegrin and Metalloprotease 33 polymorphisms and lung function decline in the general population
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DOI：
10.1183/09059180.00010121
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发表时间：
2006-12
影响因子：
7.5
通讯作者：
Cleo C. van Diemen;D. Postma;J. Vonk;M. Bruinenberg;J. Schouten;H. Marike Boezen
中科院分区：
文献类型：
--
作者：
Cleo C. van Diemen;D. Postma;J. Vonk;M. Bruinenberg;J. Schouten;H. Marike Boezen
ADAM 33（A Disintegrin and Metalloprotease 33，解整合素和金属蛋白酶33）是哮喘的易感基因，其单核苷酸多态性（single nucleotide polymorphisms，SNPs）与哮喘患者肺功能过度下降有关。评估ADAM 33中的SNPs是否与普通人群和慢性阻塞性肺疾病（COPD）的加速肺功能丧失相关。我们收集了来自Vlagtwedde/Vlaardingen队列的受试者的DNA，这些受试者在随访25年后参加了1989/1990年的最后一次调查。每3年收集一次信息，包括肺功能测量。我们在上次调查中将COPD定义为GOLD 2级或更高。对来自队列的1390名受试者进行了ADAM 33中以下SNP的基因分型：F+1、Q-1、S_1、S_2、T_1、T_2、V_4、ST+5。用卡方检验分析SNP流行率的差异。采用线性混合效应模型分析不同基因型FEV 1下降情况。在整个人群中，女性和男性的平均校正下降量分别为18.7和12.7 ml·y−1。与野生型相比，SNPs S_2和Q-1次要等位基因纯合子和SNPs S_1杂合子个体的FEV 1下降速度显著加快，分别为4.9、9.6和3.6 ml·y-1。我们发现COPD患者中F+1、S_1、S_2和T_2的SNPs的患病率显著较高。我们证明了ADAM 33中的SNPs与普通人群中肺功能的加速下降相关。这些SNP也是COPD的危险因素。
ADAM33 (A Disintegrin and Metalloprotease 33) has been identified as a susceptibility gene for asthma and single nucleotide polymorphisms (SNPs) in this gene have been associated with excess decline of lung function in asthmatics. To assess whether SNPs in ADAM33 are associated with accelerated lung function loss in the general population and with chronic obstructive pulmonary disease (COPD). We have collected DNA from subjects of the Vlagtwedde/Vlaardingen cohort participating in the last survey in 1989/1990 after a follow up of 25 years. Information was collected every 3 years, including lung function measurements. We defined COPD as GOLD stage 2 or higher at the last survey. 1390 subjects from the cohort were genotyped for the following SNPs in ADAM33: F+1, Q−1, S_1, S_2, T_1, T_2, V_4, ST+5. Differences in prevalence of SNPs were analyzed with chi-square tests. Linear mixed effects models were used to analyze FEV1 decline according to genotype. In the whole population mean adjusted decline was 18.7 and 12.7 ml·y−1 in females and males respectively. Individuals homozygous for minor alleles of SNPs S_2 and Q−1 and heterozygous for SNP S_1 had a significantly accelerated decline in FEV1 of respectively 4.9, 9.6 and 3.6 ml·y−1 compared with wild type. We found a significantly higher prevalence of SNPs F+1, S_1, S_2 and T_2 in subjects with COPD. We demonstrated that SNPs in ADAM33 are associated with accelerated lung function decline in the general population. These SNPs are also risk factors for COPD.