Department of Medical Genetics, School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
Department of Pediatrics, School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
Pediatr Pulmonol. 2018 Jul;53(7):888-900. doi: 10.1002/ppul.24005. Epub 2018 Apr 10.
Cystic fibrosis (CF) is due to dysfunction of the CFTR channel and function of this channel is, in turn, affected by modifier genes that can impact the clinical phenotype. In this context, we analyzed the interaction among rs3788766SLC6A14, rs7512462SLC26A9, rs17235416SLC11A1, and rs17563161SLC9A3 variants, CFTR mutations and 40 CF severity markers by the Multifactor Dimensionality Reduction (MDR) model.
A total of 164 patients with CF were included in the study. The variants in the modifier genes were identified by real-time PCR and the genotype of the CFTR gene in the diagnostic routine. Analysis of interaction between variants, CFTR mutations groupings and demographic, clinical and laboratory data were performed by the MDR.
There were interaction between the rs3788766, rs7512462, rs17235416, and rs17563161 variants, and CFTR mutations with pancreatic insufficiency (PI), onset of digestive symptoms, and presence of mucoid Pseudomonas aeruginosa. Regarding PI, the interaction was observed for CFTRrs17563161 (P-value = 0.015). Also, for onset of digestive symptoms the interaction was observed for CFTRrs3788766rs7512462rs17235416rs17563161 (P-value = 0.036). Considering the presence of mucoid P. aeruginosa, the interaction occurred for CFTRrs3788766rs7512462rs17563161 (P-value = 0.035).
Interaction between variants in the SLC family genes and the grouping for CFTR mutations were associated with PI, onset of digestive symptoms and mucoid P. aeruginosa, being important to determine one of the factors that may cause the diversity among the patients with CF.
囊性纤维化（CF）是由于 CFTR 通道功能障碍引起的，而该通道的功能又受到修饰基因的影响，这些修饰基因可能影响临床表型。在这种情况下，我们通过多因子降维（MDR）模型分析了 rs3788766SLC6A14、rs7512462SLC26A9、rs17235416SLC11A1 和 rs17563161SLC9A3 变体、CFTR 突变与 40 种 CF 严重程度标志物之间的相互作用。
本研究共纳入 164 例 CF 患者。通过实时 PCR 鉴定修饰基因中的变异，通过常规诊断 CFTR 基因的基因型。通过 MDR 分析变体、CFTR 突变分组与人口统计学、临床和实验室数据之间的相互作用。
rs3788766、rs7512462、rs17235416 和 rs17563161 变体与 CFTR 突变与胰腺功能不全（PI）、消化症状开始和粘脓性铜绿假单胞菌的存在之间存在相互作用。对于 PI，CFTRrs17563161 的相互作用（P 值=0.015）。同样，对于消化症状的开始，CFTRrs3788766rs7512462rs17235416rs17563161 的相互作用（P 值=0.036）。考虑到粘脓性铜绿假单胞菌的存在，CFTRrs3788766rs7512462rs17563161 的相互作用（P 值=0.035）。
SLC 家族基因变体之间的相互作用以及 CFTR 突变的分组与 PI、消化症状的开始和粘脓性铜绿假单胞菌有关，这对于确定 CF 患者之间多样性的一个可能原因非常重要。
