Background: Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasians, caused by mutation in cystic fibrosis transmembrane conductance regulator (CFTR). The analysis of some extra and intragenic markers within or closely linked to CFTR gene is useful as a molecular method in clinical linkage analysis. Indeed, knowing that the molecular basis of CF is highly heterogeneous in our population is explained in the present study. In this work, we are interested for the first time to study the polymorphic marker IVS6a GATT in a CF Tunisian population.
Methods: Our study involved 80 CF Tunisian patients with a positive sweat test. A cohort of 90 healthy controls was also enrolled. The analysis of the variant IVS6a GATT was conducted by analysis of the fragments on automatic sequencer (ABI Prism 310). A statistical analysis was performed on Statistical Package for the Social Sciences (SPSS) version 20 software.
Results: The analysis of genotypic distribution of IVS6aGATT showed a significant difference between the control and CF groups suggesting the involvement of this marker in cystic fibrosis. Furthermore, we noted that the 6 GATT repetition in the homozygous state is more common in CF patients than in the control group (p <0.05). This while the 7GATT/7GATT genotype is more common among controls compared to CF patients (p = 0.002). Regarding the interest of this polymorphism on the clinical expression of cystic fibrosis, we have noted no significant association between 6/6 genotype with different clinical conditions in CF patients outside the CFTR mutation. While a significant association was found between respiratory involvement and mixed (respiratory and digestive) and the 6/6 genotype in patients with the mutation F508del homozygous (p <0.05). In addition, a significant association was also noted with gastrointestinal involvement for non F508del patients/F508del not (p = 0.014). Given that, phenotypic and genotypic heterogeneity of cystic fibrosis, several studies have sought to highlight the role of genetic markers linked to the CFTR gene in the expression and evolution of the disease.
Conclusion: Our study on the implication of polymorphic marker IVS6a GATT is one of the first works carried out in the Tunisian population and confirms the usefulness of this marker in the clinical expression of cystic fibrosis.
Keywords: CFTR gene; F508del mutation; IVS6A GATT marker; Tunisian population; phenotypic variability.