Association analysis of the surfactant protein-C gene to childhood asthma.

Objectives: This study aims to describe the molecular variability in the gene in a childhood chronic respiratory disease, asthma, in the Tunisian population and to identify the implications based on a case-control study of p.Thr138Asn (T138N) and p.Ser186Asn (S186N) variants.

Methods: We used direct sequencing for the genotyping of the gene within 101 asthmatic children. The study of T138N and S186N variants in 110 controls is conducted by the PCR-RFLP technique.

Results: The molecular study revealed 26 variants including 24 intronic variations and 2 exonic variations (T138N and S186N) with respective frequencies of 16.8% and 18.3%. We conducted a case-control study of the two identified exonic variations. A different genotypic and allelic distribution between the two groups was noted. Only the T138N polymorphism showed a significant association with asthma disease ( < 1 0 ). Statistical analysis elaborated four haplotypes with the following frequencies in patients vs controls: 138Thr-186Ser (79.5% vs 57.6%), 138Thr-186Asn (3.7% vs 7.8%), 138Asn-186Thr (2.2% vs 20.2%) and 138Asn-186Asn (14.6% vs 14.4%). A significant difference ( < 1 0 ) was highlighted in haplotype distribution. The 138Asn-186Ser (OR [95%CI] = 0.14[0.04-0.54],  = 0.004, R=0.93) and 138Thr-186Asn (OR [95%CI] = 0.35[0.12-0.54],  = 0.047, R=0.88) haplotypes showed a negative association with asthma which may constitute a protective factor against the disease.

Conclusion: In Tunisia, this work constitutes the first report interested in the gene and highlights the genetic variability of the gene in asthma. Therefore, the case-controls analysis may be useful in the study of surfactant proteins dysfunction in chronic respiratory disease at an early age.