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

Abstract

Objectives

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.

Methods

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.

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 (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.

Conclusion

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.

KEYWORDS:

• SFTPC gene
• genetic association
• childhood asthma
• haplotype

Acknowledgements

We thank Annick Le Floch for her expert technical assistance and Dr Alix de Becdelièvre for helpful discussion (Genetic Department, Henri Mondor Hospital).

We would like to thank Mr. Samson Bush, English teacher at the ADRA_Tunisia organization ([email protected]) and Mr. Ronald Wallace, English teacher at Amideast_Tunisia and Wall Street_Tunisia centers (email address: [email protected]) for English editing of the manuscript.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This work was supported by a Grant from the Research Laboratory (LR00SP03) ‘‘Ministry of Higher Education and Scientific Research’’ of Tunisia.