Center for Investigation in Pediatrics, Faculty of Medical Sciences, University of Campinas, Tessália Vieira de Camargo, 126, Cidade Universitária "Zeferino Vaz", CEP: 13083-887 Campinas, São Paulo, Brazil.
BMC Med Genet. 2014 Mar 4;15:27. doi: 10.1186/1471-2350-15-27.
Cystic fibrosis (CF) clinically manifests with various levels of severity, which are thought to be modulated by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR), modifier genes, and the environment. This study verified whether polymorphisms in modifier genes associated with glutathione (GSH) metabolism influence CF severity.
A cross-sectional study of 180 CF patients was carried out from 2011 to 2012. We analyzed CFTR mutations, polymorphisms (GSTM1 and GSTT1 deletions, GSTP1 + 313A > G, GCLC-129C > T, and GCLC-3506A > G) in modifier genes and CF clinical severity as assessed by 28 clinical and laboratory variables.
Significant associations were found between modifier gene polymorphisms and particular phenotypes or genotype changes. These included GCLC-129C > T with a higher frequency of the Pseudomonas aeruginosa mucoid to CC genotype (p = 0.044), and GCLC-3506A > G with a higher frequency of the no-mucoid P. aeruginosa (NMPA) to AA genotype (p = 0.012). The GSTT1 deletion was associated with a higher frequency of the NMPA to homozygous deletion (p = 0.008), GSTP1 + 313A > G with a minor risk of osteoporosis (p = 0.036), and patient age ≤ 154 months (p = 0.044) with the AA genotype. The Bhalla score was associated with GCLC-3506A > G (p = 0.044) and GSTM1/GSTT1 deletion polymorphisms (p = 0.02), while transcutaneous hemoglobin oxygen saturation levels were associated with GSTT1 deletions (p = 0.048).
CF severity is associated with polymorphisms in GSH pathways and CFTR mutations.
囊性纤维化（CF）在临床上表现出不同程度的严重程度，据认为这些严重程度是由囊性纤维化跨膜电导调节因子（CFTR）基因突变、修饰基因和环境共同调节的。本研究旨在验证与谷胱甘肽（GSH）代谢相关的修饰基因多态性是否会影响 CF 的严重程度。
本研究于 2011 年至 2012 年进行了一项 180 例 CF 患者的横断面研究。我们分析了 CFTR 突变、修饰基因多态性（GSTM1 和 GSTT1 缺失、GSTP1+313A>G、GCLC-129C>T 和 GCLC-3506A>G）与 28 项临床和实验室变量评估的 CF 临床严重程度之间的关系。
修饰基因多态性与特定表型或基因型变化之间存在显著相关性。具体包括：GCLC-129C>T 与铜绿假单胞菌粘液表型 CC 基因型的更高频率有关（p=0.044），GCLC-3506A>G 与非粘液型铜绿假单胞菌（NMPA）AA 基因型的更高频率有关（p=0.012）。GSTT1 缺失与 NMPA 纯合缺失的更高频率有关（p=0.008），GSTP1+313A>G 与骨质疏松症的较小风险（p=0.036）以及年龄≤154 个月的患者有关（p=0.044）AA 基因型。Bhalla 评分与 GCLC-3506A>G（p=0.044）和 GSTM1/GSTT1 缺失多态性（p=0.02）有关，而经皮血红蛋白氧饱和度水平与 GSTT1 缺失有关（p=0.048）。
CF 严重程度与 GSH 途径和 CFTR 基因突变的多态性有关。
