The Adult Cystic Fibrosis Centre, The Prince Charles Hospital, 4032, Queensland, Australia; School of Medicine, University of Queensland, 4029, Queensland, Australia; Lung Infection and Inflammation Laboratory, QIMR Berghofer Medical Research Institute, 4029, Queensland, Australia.
Cancer and Population Studies, QIMR Berghofer Medical Research Institute, 4029, Queensland, Australia.
Gene. 2019 Jan 30;683:12-17. doi: 10.1016/j.gene.2018.10.002. Epub 2018 Oct 3.
Genetic modifiers contribute to variable disease phenotype in cystic fibrosis (CF). We explored the association between mutations in the hemochromatosis (HFE) gene and disease severity in adults with CF.
HFE genotyping was performed in 163 adults with CF attending a single centre. Results were correlated with lung disease severity, prevalence of CF-related diabetes (CFRD) and history of meconium ileus (MI) or distal intestinal obstruction syndrome (DIOS).
Subjects with the C282Y substitution in the HFE protein (C282Y mutation) had a lower FEV percentage predicted (54% versus 66%, p = 0.029) and accelerated rate of FEV decline (-110 mL versus -80 mL per year respectively, p < 0.001) compared to subjects with a normal HFE genotype. C282Y substitutions were associated with increased rates of CFRD (58% versus 33%, p = 0.026) and a trend towards increased MI or DIOS (38% versus 19%, p = 0.05). H63D HFE substitutions were associated with a more rapid rate of decline in forced vital capacity (p = 0.01) and increased risk of MI or DIOS (p = 0.02).
In subjects with CF, the C282Y HFE substitution was associated with worse lung function, and increased rates of CFRD and gastrointestinal complications. The H63D HFE substitution also impacted on disease phenotype, but to a lesser extent. The results support a role for HFE gene mutations as modifiers of CF phenotype.
遗传修饰因子导致囊性纤维化（CF）患者的疾病表型存在差异。本研究旨在探讨血色病（HFE）基因突变与成年 CF 患者疾病严重程度之间的关系。
对在单一中心就诊的 163 名 CF 成年患者进行 HFE 基因分型。结果与肺部疾病严重程度、CF 相关糖尿病（CFRD）的发生率以及先天性肠梗阻（MI）或远端小肠梗阻综合征（DIOS）病史相关联。
HFE 蛋白 C282Y 取代（C282Y 突变）患者的 FEV1%预计值较低（54%对 66%，p=0.029），FEV1 下降速度更快（分别为-110mL/年和-80mL/年，p<0.001）。与正常 HFE 基因型患者相比，C282Y 取代与 CFRD 发生率升高（58%对 33%，p=0.026）和 MI 或 DIOS 的发生率呈上升趋势（38%对 19%，p=0.05）相关。H63D HFE 取代与用力肺活量下降速度更快相关（p=0.01），且 MI 或 DIOS 的风险增加（p=0.02）。
在 CF 患者中，C282Y HFE 取代与肺功能下降更严重、CFRD 和胃肠道并发症发生率增加相关。H63D HFE 取代也对疾病表型有影响，但程度较轻。这些结果支持 HFE 基因突变作为 CF 表型修饰因子的作用。
