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

Autor(es)

Pereira, Stephanie Villa-Nova ^[1] ; Ribeiro, Jose Dirceu ^{[2, 3]} ; Bertuzzo, Carmen Silvia ^[1] ; Lima Marson, Fernando Augusto ^{[2, 3, 1]}

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Fac Med Sci, Dept Med Genet, Tessalia Vieira de Camargo, 126, Barao Geraldo, BR-13083887 Campinas, SP - Brazil

^[2] Univ Estadual Campinas, Fac Med Sci, Dept Pediat, Tessalia Vieira de Camargo, 126, Barao Geraldo, BR-13083887 Campinas, SP - Brazil

^[3] Univ Estadual Campinas, Fac Med Sci, Ctr Pediat Invest, Lab Pulm Physiol, Tessalia Vieira de Camargo, 126, Barao Geraldo, BR-13083887 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Gene; v. 629, p. 117-126, SEP 20 2017.
• Citações Web of Science: 16

Resumo

Introduction: Cystic fibrosis (CF) manifests with clinical and histopathological variability depending on environmental and genetic factors. Moreover, the genes encoding ion channels{[}rs3788766(SLC6A/4), 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%Cl = 0.029-0.696), non-mucoid P. aeruginosa (OR = 0.283; 95%CI = 0.094-0.853) and Staphyloccocus aureus (OR = 4.443; 95%Cl = 1.019-40.64), largest FEFmax(p = 0.041) and best response to bronchodilator for FEE50%(P = 0.033) and FEV1/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 FEFmax(p = 0.028) and FEF25%(P = 0.031) values; (iv) rs7512462{*}CC with highest Shwachman-Kulczycki score (p = 0.019), FVC(p = 0.043), FEV1(p = 0.047), FEV1/FVC(p = 0.022), FEF50%(P = 0.038) and FEF25-754P = 0.016); (v) rs7512462{*}CT with lowest values of FVC(p = 0.034), FEV1(p = 0.047), FEV1/FVC(p = 0.022), FEF25%(p = 0.012), FEF50%(P = 0.038), FEF75%(P = 0.008), FEF25-75%(p = 0.016) and ERV(p = 0.023); (vi) rs7512462{*}TT with best response to the inhaled bronchodilator for FEV1(p = 0.011), FEE50%(P = 0.019), FEF75%(p = 0.036) and FEF25-75%(P = 0.008); (vii) rs17234516{*}Normal allele with lowest value of SaO(2) (p = 0.010) and S. aureus (OR = 3.333; 95%Cl = 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. (AU)

• Processo FAPESP: 11/12939-4 - Associação entre polimorfismos de genes moduladores em crianças e adolescentes com asma alérgica e não alérgica: leve, moderada e grave
• Beneficiário: Fernando Augusto de Lima Marson
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 15/12183-8 - Identificação das mutações prevalentes e caracterização clínica e funcional de crianças e adultos com discinesia ciliar primária
• Beneficiário: Jose Dirceu Ribeiro
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/18845-1 - Associação entre polimorfismos de genes moduladores em crianças e adolescentes com asma alérgica e não alérgica leve, moderada e grave
• Beneficiário: Jose Dirceu Ribeiro
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/12858-5 - Identificação das mutações prevalentes e caracterização clínica e funcional de crianças e adultos com discinesia ciliar primária
• Beneficiário: Fernando Augusto de Lima Marson
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado