Abstract Background There is an association between persistent preschool wheezing phenotypes and school‐age asthma. These wheezing/asthma phenotypes likely represent clinical entities having specific genetic risk factors. The SERPINA1 gene encodes α 1 ‐antitrypsin (AAT), and mutations in the gene are important in the pathophysiology of pulmonary diseases. We hypothesized that there might be an association between SERPINA1 gene polymorphisms and the risk of developing wheezing/school age asthma. Objective To examine 10 single nucleotide polymorphisms (SNPs) of SERPINA1 (rs6647, rs11832, rs17580, rs709932, rs1243160, rs2854254, rs8004738, rs17751769, rs28929470, and rs28929474) and relate them to childhood wheezing phenotypes and doctor‐diagnosed asthma in the population‐based Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Methods Wheeze data, reports of physician‐diagnosed asthma and data on the SERPINA1 gene SNPs, were available for 7964 children. Binary logistic regression was used to assess the associations between allele prevalence and wheezing and asthma phenotypes. P values were adjusted to account for multiple hypotheses using the Benjamini‐Hochberg false discovery rate. Results Only within a subgroup of children with asthma who had no prior diagnosis of preschool wheeze was there a trend for association between rs28929474 (Glu342Lys, Pi*Z causing AAT deficiency; P = .0058, adjusted P = .058). No SNP was associated with wheezing and asthma in those with preschool wheeze. Conclusion Analyzed SNPs in SERPINA1 are not associated with wheezing/asthma phenotypes. Only rs28929474, the most common pathologic SNP (Pi*Z) in the SERPINA1 gene, might be associated with a risk of developing school‐age asthma without exhibiting preschool wheeze.