Polymorphisms in A disintegrin and metalloprotease 33 (ADAM33) predict impaired early-life lung function
Polymorphisms in A disintegrin and metalloprotease 33 (ADAM33) predict impaired early-life lung function
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DOI：
10.1164/rccm.200412-1708oc
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发表时间：
2005-07-01
影响因子：
24.7
通讯作者：
John, SL
中科院分区：
文献类型：
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作者：
Simpson, A;Maniatis, N;John, SL
理论基础：哮喘通常起源于生命早期，与肺功能受损有关，而肺功能受损可追溯到成年。目的：在一项前瞻性出生队列研究的背景下，我们调查了去整合素和金属蛋白酶33(ADAM33)基因的单核苷酸多态(SNPs)与早期肺功能的关系。方法：对儿童ADAM33基因的17个SNPs进行基因分型。分别在3岁(n=285)和5岁(n=470)时用体积描记法测量比气道阻力(SRAW)来评估肺功能。在5岁时，我们还测量了FEV1。用Logistic回归分析SNPs，然后用连锁不平衡作图来确定因果基因座。主要结果：F+1SNP罕见等位基因携带者在3岁时肺功能下降(p=0.003)。当考虑隐性模型时，有4个SNPs(F+1、S1、ST+5、V4)在5岁时与SRAW相关(p<；0.04)。利用连锁不平衡作图，我们发现了BC+1和F1 SNPs之间存在显著因果位置的证据，位于该基因的S末端。有4个SNP与FEV1降低相关(F+1、M+1、T1和T2；p
Rationale: Asthma commonly originates in early life in association with impaired lung function, which tracks to adulthood. Objectives: Within the context of a prospective birth cohort study, we investigated the association between single nucleotide polymorphisms (SNPs) in a disintegrin and metalloprotease 33 (ADAM33) gene and early-life lung function. Methods: Children were genotyped for 17 SNPs in ADAM33. Lung function at age 3 (n = 285) and 5 years (n = 470) was assessed using plethysmographic measurement of specific airway resistance (sRaw). At age 5, we also measured FEV1. SNPs were analyzed individually using logistic regression, followed by linkage disequilibrium mapping to identify the causal locus. Main Results: Carriers of the rare allele of F+1 SNP had reduced lung function at age 3 years (p = 0.003). When the recessive model was considered, four SNPs (F + 1, S1, ST + 5, V4) showed association with sRaw at age 5 years (p < 0.04). Using linkage disequilibrium mapping, we found evidence of a significant causal location between BC + 1 and F1 SNPs, at the S' end of the gene. Four SNPs were associated with lower FEV1 (F + 1, M + 1, T1, and T2; p