CC16 genotype frequencies: Differences between two western Australian populations

An adenine to guanine substitution at position 38 of the Clara cell secretory protein (CC16) gene (A38G) has shown an association between the 38A genotype and an increased risk of asthma. Aim: To compare the A38G genotype frequency, and identify possible associations between the A38G genotype, asthma and lung function parameters in two Western Australian (WA) populations. Subjects: (1) 266 individuals from 76 nuclear families living in Perth, and (2) 237 individuals from an isolated indigenous community in the tropical north of WA. Genomic methods: PCR products of the CC16 exon 1 were genotyped by Sau 96 I restriction digestion which were confirmed in 10% of the samples by DMA sequencing. Results: Population 1 had 27 (10.2%) homozygous for the published sequence (38A/38A), 123 (46.2%) were heterozygous (38A/38G), and 116 (43.6%) were homozygous for the polymorphism (38G/38G). In contrast, population 2 had 149 (62.9%) with 38A/38A, 75 (31.6%) 38A/38G, and only 13 (5.5%) with the 38G/38G genotype. An association was observed between the 38A allele and an increased risk of asthma in population 1 (p=0.02). In population 2, the 38AAM genotype was associated with reduced FEVi (p=0.033). Conclusions: The marked difference in the CC16 genotype frequencies between the two populations may be due to environmental selective pressures, but is more likely a consequence of founder effect and random genetic drift. Despite these differences, this work provides evidence from both populations that the 38A allele may be associated with an increased risk of expressing asthma-related traits. We gratefully acknowledge all the people who participated in this study.