Association between the CC16 polymorphism A38G and asthma in an unselected australian population

The Clara cell secretory protein (CC16) gene, is located on chromosome 11q13, has several anti-inflammatory properties and is one of the most abundant proteins produced in the airway. We have previously described an adenine to guanine substitution at position 38 (A38G) in the CC16 gene, and, in a small population, have shown an increased risk of asthma for individuals homozygous for 38A compared to those homozygous for 38G. Aims: To confirm that the A38G polymorphism is associated with the asthma phenotype using a larger, unselected cohort on which there is extensive clinical and immunological data. Methods: A cohort of 718 individuals were originally selected in 1982 as 8 year olds from a general population in Belmont, New South Wales. Recent follow-up assessment in 1997 included questionnaire, spirometry, histamine challenge and skin prick testing. Subjects were classified as having asthma on the basis of a physician diagnosis in this survey. Blood was collected and DMA extracted for genotyping. The A38G genotype of 123 subjects was determined using Sau 96 I restriction digestion of CC16 exon I PCR products. Results: 10.6% were homozygous for the GENBANK sequence (38A), 58.5% heterozygous and 30.9% homozygous for the 38G sequence. Logistic regression analysis showed that subjects homozygous for 38A had a 3.5 fold increased risk of asthma (95% confidence interval 1.08-11.32, p=0.037) compared with heterozygous and homozygous 38G individuals. Conclusion: These results support the previous findings that the 38A allele increases the risk of an individual developing asthma.