Association of clinical severity of cystic fibrosis with variants in the SLC gene family (SLC6A14, SLC26A9, SLC11A1 and SLC9A3).

Introduction: Cystic fibrosis (CF) manifests with clinical and histopathological variability depending on environmental and genetic factors. Moreover, the genes encoding ion channels[rs3788766(SLC6A14), rs7512462(SLC26A9), rs17235416(SLC11A1) and rs17563161(SLC9A3)] have been insufficiently studied as modifier genes. Then, our objective was associate the variants in the genes of SLC family with 43 CF severity markers.

Methods: The variants were identified by real-time-PCR in 188 CF patients considering the CFTR genotype. Statistical analyses were performed by parametric and nonparametric tests. The correction by multiple testing was performed by the False Rate Discovery test, alpha=0.05.

Results: Depending on the CFTR mutations, we found association of: (i) rs3788766*CC with mucoid Pseudomonas aeruginosa (OR=0.171; 95%CI=0.029-0.696), non-mucoid P. aeruginosa (OR=0.283; 95%CI=0.094-0.853) and Staphyloccocus aureus (OR=4.443; 95%CI=1.019-40.64), largest FEF(p=0.041) and best response to bronchodilator for FEF(p=0.033) and FEV/FVC(p=0.044); (ii) rs3788766*CT with early start of pulmonary symptom (OR=3.524; 95%CI=1.229-10.1) and osteoporosis (OR=0.203; 95%CI=0.022-0.883); (iii) rs3788766*TT with lowest body mass index (OR=4.242; 95%CI=1.505-11.95), presence of mucoid P. aeruginosa (OR=3.176; 95%CI=1.29-7.819) and S. aureus (OR=0.116; 95%CI=0.004-0.881), highest Bhalla score (p=0.047) and lowest FEF(p=0.028) and FEF(p=0.031) values; (iv) rs7512462*CC with highest Shwachman-Kulczycki score (p=0.019), FVC(p=0.043), FEV(p=0.047), FEV/FVC(p=0.022), FEF(p=0.038) and FEF(p=0.016); (v) rs7512462*CT with lowest values of FVC(p=0.034), FEV(p=0.047), FEV/FVC(p=0.022), FEF(p=0.012), FEF(p=0.038), FEF(p=0.008), FEF(p=0.016) and ERV(p=0.023); (vi) rs7512462*TT with best response to the inhaled bronchodilator for FEV(p=0.011), FEF(p=0.019), FEF(p=0.036) and FEF(p=0.008); (vii) rs17234516*Normal allele with lowest value of SaO (p=0.010) and S. aureus (OR=3.333; 95%CI=1.085-10.24); (viii) rs17563161*GG with lowest age for onset of digestive symptoms (OR=2.564; 95%CI=1.234-5.33).

Conclusions: The clinical and laboratory variability of CF were associated with the variants in the genes of SLC family in our sample.