囊性纤维化临床严重程度与SLC基因家族（SLC6A14、SLC26A9、SLC11A1和SLC9A3）变异的关联。
Association of clinical severity of cystic fibrosis with variants in the SLC gene family (SLC6A14, SLC26A9, SLC11A1 and SLC9A3).
作者信息
Pereira Stéphanie Villa-Nova, Ribeiro José Dirceu, Bertuzzo Carmen Sílvia, Marson Fernando Augusto Lima
机构信息
Department of Medical Genetics, Faculty of Medical Sciences, State University of Campinas, Tessália Vieira de Camargo, 126, Barão Geraldo, Cidade Universitária Zeferino Vaz, 13083-887 Campinas, São Paulo, Brazil.
Department of Pediatrics, Faculty of Medical Sciences, State University of Campinas, Tessália Vieira de Camargo, 126, Barão Geraldo, Cidade Universitária Zeferino Vaz, 13083-887 Campinas, São Paulo, Brazil; Laboratory of Pulmonary Physiology, Center for Pediatrics Investigation, Faculty of Medical Sciences, State University of Campinas, Tessália Vieira de Camargo, 126, Barão Geraldo, Cidade Universitária Zeferino Vaz, 13083-887 Campinas, São Paulo, Brazil.
出版信息
Gene. 2017 Sep 20;629:117-126. doi: 10.1016/j.gene.2017.07.068. Epub 2017 Jul 27.
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) rs3788766CC 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) rs3788766CT 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) rs3788766TT 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) rs7512462CC 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) rs7512462CT 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) rs7512462TT 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) rs17234516Normal allele with lowest value of SaO (p=0.010) and S. aureus (OR=3.333; 95%CI=1.085-10.24); (viii) rs17563161GG 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.
引言
囊性纤维化（CF）的临床表现和组织病理学变化取决于环境和遗传因素。此外，作为修饰基因，编码离子通道的基因[rs3788766（SLC6A14）、rs7512462（SLC26A9）、rs17235416（SLC11A1）和rs17563161（SLC9A3）]尚未得到充分研究。因此，我们的目标是将SLC家族基因中的变异与43个CF严重程度标志物相关联。
方法
在188例CF患者中，根据CFTR基因型通过实时PCR鉴定变异。采用参数检验和非参数检验进行统计分析。通过错误率发现检验进行多重检验校正，α=0.05。
结果
根据CFTR突变，我们发现：（i）rs3788766CC与黏液型铜绿假单胞菌（OR=0.171；95%CI=0.029 - 0.696）、非黏液型铜绿假单胞菌（OR=0.283；95%CI=0.094 - 0.853）和金黄色葡萄球菌（OR=4.443；95%CI=1.019 - 40.64）相关，最大用力呼气流量（FEF）最高（p=0.041），对支气管扩张剂治疗FEF（p=0.033）和FEV/FVC（p=0.044）的最佳反应；（ii）rs3788766CT与肺部症状早期发作（OR=3.524；95%CI=1.229 - 10.1）和骨质疏松症（OR=0.203；95%CI=0.022 - 0.883）相关；（iii）rs3788766TT与最低体重指数（OR=4.242；95%CI=1.505 - 11.95）、黏液型铜绿假单胞菌存在（OR=3.176；95%CI=1.29 - 7.819）和金黄色葡萄球菌（OR=0.116；95%CI=0.004 - 0.881）相关，最高Bhalla评分（p=0.047）以及最低FEF（p=0.028）和FEF（p=0.031）值；（iv）rs7512462CC与最高Shwachman - Kulczycki评分（p=0.019）、FVC（p=0.043）、FEV（p=0.047）、FEV/FVC（p=0.022）、FEF（p=0.038）和FEF（p=0.016）相关；（v）rs7512462CT与最低的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）和ERV（p=0.023）值相关；（vi）rs7512462TT与吸入支气管扩张剂对FEV（p=0.011）、FEF（p=0.019）、FEF（p=0.036）和FEF（p=0.008）的最佳反应相关；（vii）rs17234516正常等位基因与最低的SaO值（p=0.010）和金黄色葡萄球菌（OR=3.333；95%CI=1.085 - 10.24）相关；（viii）rs17563161GG与消化症状发作的最低年龄（OR=2.564；95%CI=1.234 - 5.33）相关。
结论
在我们的样本中，CF的临床和实验室变异性与SLC家族基因中的变异相关。
Zotero 插件