A polymorphism in the NPPA gene associates with asthma
A polymorphism in the NPPA gene associates with asthma
复制标题
DOI：
10.1111/j.1365-2222.2008.02955.x
复制
发表时间：
2008-07-01
影响因子：
6.1
通讯作者：
Sylvester, J. E.
中科院分区：
文献类型：
--
作者：
Lima, J. J.;Mohapatra, S.;Sylvester, J. E.
[背景]心房利钠肽(ANP)在肺中起重要作用，在哮喘的过敏性炎症中起重要作用。目的研究ANP基因启动子上的C/G(Rs13305986)、外显子1中的G/A(Rs5063)导致NPPAMet32->、Val替换、外显子3中的T/C(Rs5065)导致Arg152->、Ter替换和3‘UT区的T/C(Rs5067)。筛查队列包括参加大型临床试验的336例哮喘患者和154例非哮喘对照组。重复队列包括来自第二次临床试验的172例哮喘患者和115名健康对照。在筛查队列中，病例和对照的人口统计学特征很好地匹配。结果在筛查和重复队列中，rs5067的C等位基因与哮喘相关，校正OR值(95%可信区间)分别为0.29~0.84(P=0.009)和0.24(0.11~0.53；P<；0.0001)。在筛查队列中，rs5065的C等位基因与哮喘相关，但在重复队列中与哮喘无关。Rs5067 C等位基因携带者发生哮喘的人群归因危险度为23.3%。结论rs5067可使筛查和复制队列中C等位基因携带者发生哮喘的风险分别降低50%和76%。NPPA可能是哮喘的重要易感基因。
Background Atria] natriuretic peptide (ANP) plays an important role in the lung and in augmenting allergic inflammation in asthma. The gene encoding ANP, NPPA, is located on chromosome 1p36, a region that has been linked to asthma.Objectives Determine associations between asthma and four common SNPs on the NPPA gene: C/G (rs13305986) in the promoter; G/A (rs5063) in Exon 1 resulting in NPPAMet32 --> Val substitution; T/C (rs5065) in Exon 3 resulting in an Arg152 --> Ter substitution; and T/C in the 3'UT region (rs5067).Methods A case-control design was used in White participants. The screening cohort consisted of 336 asthmatic cases who participated in a large clinical trial and 154, non-asthmatic controls. The replicate cohort consisted of 172 asthmatic cases from a second clinical trial and 115 healthy controls. Demographic characteristics were well matched for cases and controls in the screening cohort. Adjusted (age, gender, body mass index) odds ratio 2 (OR) were calculated by chi(2) and logistic regression; a P-value of 0.0167 defined the threshold of significance.Results The C allele of rs5067 was associated with asthma in the screening and replicate cohorts: adjusted ORs (95% confidence intervals) 0.5 (0.29-0.84; P = 0.009) and 0.24 (0.11-0.53; P < 0.0001), respectively. The C allele of rs5065 was associated with asthma in the screening cohort but not in the replicate. The population-attributable risk for asthma in carriers of the C allele for rs5067 was 23.3%.Conclusions For rs5067, the risks of asthma in carriers of the C allele in the screening and replicate cohorts were reduced by 50% and 76%, respectively. NPPA may be an important susceptibility gene for asthma.