Waeber G, Haefliger J A
Département de Médecine Interne B, CHUV, Lausanne.
Schweiz Med Wochenschr. 1997 Mar 29;127(13):554-60.
The relative importance of molecular biology in clinical practice is often underestimated. However, numerous procedures in clinical diagnosis and new therapeutic drugs have resulted from basic molecular research. Furthermore, understanding of the physiological and physiopathological mechanisms underlying several human diseases has been improved by the results of basic molecular research. For example, cloning of the gene encoding leptin has provided spectacular insights into the understanding of the mechanisms involved in the control of food intake and body weight maintenance in man. In cystic fibrosis, the cloning and identification of several mutations in the gene encoding the chloride channel transmembrane regulator (CFTR) have resolved several important issues in clinical practice: cystic fibrosis constitutes a molecular defect of a single gene. There is a strong correlation between the clinical manifestations or the severity of the disease (phenotype) with the type of mutations present in the CFTR gene (genotype). More recently, identification of mutations in the gene encoding a subunit of the renal sodium channel in the Liddle syndrome has provided important insight into the physiopathological understanding of mechanisms involved in this form of hereditary hypertension. Salt retention and secondary high blood pressure are the result of constitutive activation of the renal sodium channel by mutations in the gene encoding the renal sodium channel. It is speculated that less severe mutations in this channel could result in a less severe form of hypertension which may correspond to patients suffering from high blood pressure with low plasma renin activity. Several tools, most notably PCR, are derived from molecular research and are used in everyday practice, i.e. in prenatal diagnosis and in the diagnosis of several infectious diseases including tuberculosis and hepatitis. Finally, the production of recombinant proteins at lower cost and with fewer side effects is used in everyday clinical practice. Gene therapy remains an extraordinary challenge in correcting severe hereditary or acquired diseases. The use of genetically modified animal cell lines producing growth factors, insulin or erythropoetin, which are subsequently encapsulated and transferred to man, represents an attractive approach for gene therapy.
分子生物学在临床实践中的相对重要性常常被低估。然而，临床诊断中的众多程序和新型治疗药物都源于基础分子研究。此外，基础分子研究的成果增进了我们对多种人类疾病背后生理和病理生理机制的理解。例如，瘦素编码基因的克隆为理解人类食物摄入控制和体重维持机制提供了惊人的见解。在囊性纤维化中，编码氯离子通道跨膜调节因子（CFTR）基因的多个突变的克隆和鉴定解决了临床实践中的几个重要问题：囊性纤维化是单个基因的分子缺陷。CFTR基因中存在的突变类型与疾病的临床表现或严重程度（表型）之间存在很强的相关性。最近，利德尔综合征中编码肾钠通道亚基基因的突变鉴定，为这种遗传性高血压形式所涉及机制的病理生理理解提供了重要见解。钠潴留和继发性高血压是肾钠通道编码基因突变导致肾钠通道持续激活的结果。据推测，该通道中不太严重的突变可能导致较轻形式的高血压，这可能对应于血浆肾素活性低的高血压患者。几种工具，最显著的是聚合酶链反应（PCR），源自分子研究并用于日常实践，即在产前诊断以及包括结核病和肝炎在内的几种传染病的诊断中。最后，以更低成本和更少副作用生产重组蛋白被用于日常临床实践。基因治疗在纠正严重遗传性或获得性疾病方面仍然是一项巨大挑战。使用产生生长因子、胰岛素或促红细胞生成素的基因修饰动物细胞系，随后将其封装并转移给人类，是一种有吸引力的基因治疗方法。
