Duthie A, Doherty D G, Williams C, Scott-Jupp R, Warner J O, Tanner M S, Williamson R, Mowat A P
Department of Child Health, King's College Hospital, London, United Kingdom.
Hepatology. 1992 Apr;15(4):660-4. doi: 10.1002/hep.1840150418.
Genetic factors have been implicated in the pathogenesis of liver disease in cystic fibrosis. To investigate whether liver disease is associated with particular mutations of the defective gene in cystic fibrosis, we have determined the frequencies of three mutations--delta F508, G551D and R553X--in 111 children and young adults with cystic fibrosis by analysis of genomic DNA segments amplified by the polymerase chain reaction. Twenty-nine patients had severe liver disease with portal hypertension, 19 had clinical and/or biochemical evidence of liver disease but no associated portal hypertension and 63 had no evidence of liver disease. No significant differences in the frequencies of the delta F508, G551D or R553X mutations in the three clinical subgroups were found, and we conclude that the development of liver disease in cystic fibrosis is unlikely to be associated with a specific mutation in the gene. However, because 27% of cystic fibrosis chromosomes do not have a defined mutation, this possibility cannot be ruled out. A familial concordance for clinical liver disease of 20% in this study, compared with a reported prevalence of 4.7%, suggests that genes outside the cystic fibrosis locus and/or environmental factors are involved in the pathogenesis of liver disease in cystic fibrosis.
遗传因素已被认为与囊性纤维化肝病的发病机制有关。为了研究肝病是否与囊性纤维化缺陷基因的特定突变相关，我们通过分析经聚合酶链反应扩增的基因组DNA片段，测定了111例患有囊性纤维化的儿童和年轻人中三种突变——ΔF508、G551D和R553X——的频率。29例患者患有伴有门静脉高压的严重肝病，19例有肝病的临床和/或生化证据但无相关门静脉高压，63例无肝病证据。在三个临床亚组中，未发现ΔF508、G551D或R553X突变频率有显著差异，我们得出结论，囊性纤维化肝病的发生不太可能与该基因的特定突变相关。然而，由于27%的囊性纤维化染色体没有明确的突变，这种可能性不能排除。本研究中临床肝病的家族一致性为20%，而报道的患病率为4.7%，这表明囊性纤维化位点以外的基因和/或环境因素参与了囊性纤维化肝病的发病机制。
