A polymorphism in the NPPA gene associates with asthma

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.