SERPINA1 gene polymorphisms in a population-based ALSPAC cohort

Area of Science:

• Genetics
• Pulmonology
• Pediatrics

Background:

• Persistent wheezing in preschoolers is associated with school-age asthma.
• The SERPINA1 gene, encoding alpha 1-antitrypsin (AAT), is implicated in pulmonary diseases.
• Genetic factors may influence the risk of developing wheezing and asthma phenotypes.

Purpose of the Study:

• To investigate the association between 10 single nucleotide polymorphisms (SNPs) in the SERPINA1 gene and childhood wheezing phenotypes.
• To determine if SERPINA1 gene variations are linked to doctor-diagnosed asthma in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort.

Main Methods:

• Examined 10 SERPINA1 gene SNPs (rs6647, rs11832, rs17580, rs709932, rs1243160, rs2854254, rs8004738, rs17751769, rs28929470, rs28929474).
• Utilized binary logistic regression to analyze associations between allele prevalence and wheezing/asthma phenotypes in 7964 children.
• Adjusted P-values using the Benjamini-Hochberg false discovery rate for multiple hypotheses.

Main Results:

• No significant association was found between the analyzed SERPINA1 SNPs and wheezing or asthma in children with preschool wheeze.
• A trend for association was observed between rs28929474 (Pi*Z variant) and asthma in children without a prior preschool wheeze diagnosis (adjusted P = 0.058).

Conclusions:

• The studied SERPINA1 gene polymorphisms are not generally associated with wheezing or asthma phenotypes in children.
• The rs28929474 SNP (Pi*Z) may potentially be linked to the risk of developing school-age asthma in the absence of preschool wheeze.