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

This study aims to describe the molecular variability in the SFTPC 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.

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

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 (p < 1 0 ^-3). 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 (p < 1 0 ^-3) was highlighted in haplotype distribution. The 138Asn-186Ser (OR [95%CI] = 0.14[0.04-0.54], p = 0.004, R²=0.93) and 138Thr-186Asn (OR [95%CI] = 0.35[0.12-0.54], p = 0.047, R²=0.88) haplotypes showed a negative association with asthma which may constitute a protective factor against the disease.

In Tunisia, this work constitutes the first report interested in the SFTPC gene and highlights the genetic variability of the SFTPC 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.