囊性纤维化表型变异与修饰基因关系的研究进展
Research Progress of the Relationship between Phenotypic Variability and Modifier Genes in Cystic Fibrosis
DOI: 10.12677/acm.2024.1451458, PDF,   
作者: 杨 恬, 田代印*：重庆医科大学附属儿童医院呼吸科，国家儿童健康与疾病临床医学研究中心，儿童发育疾病研究教育部重点实验室，儿童感染与免疫罕见病重庆市重点实验室，重庆
关键词: 囊性纤维化；囊性纤维化跨膜传导调节因子；基因突变；表型变异；修饰基因；Cystic Fibrosis； Cystic Fibrosis Transmembrane Conductance Regulator； Gene Mutation； Phenotypic Variability； Modifier Genes
摘要: 囊性纤维化(cystic fibrosis, CF)是由囊性纤维化跨膜传导调节因子(cystic fibrosis transmembrane conductance regulator, CFTR)基因突变引起的一种单基因常染色体隐性遗传病，可引起多个器官系统受累。尽管囊性纤维化临床表型与基因突变种类相关，但即使具有相同突变的个体，也可有不同的疾病表现，而有研究表明修饰基因在这其中起到了关键作用，特别是在囊性纤维化肺部疾病方面。本文就囊性纤维化表型变异与修饰基因关系的相关研究进行综述，并主要介绍肺部表型变异相关的修饰基因。
Abstract: Cystic fibrosis (CF) is a single gene autosomal recessive condition caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which can cause multiple organ system involvement. Although the cystic fibrosis clinical phenotype is associated with a variety of gene mutations, even individuals with the same mutation can have different disease manifestations, and there are studies suggesting that modifier genes play a key role in this, particularly in cystic fibrosis lung diseases. In this review, we focus on the relationship between CF phenotype and modifier genes, and mainly introduce the modifier genes related to CF lung diseases.
文章引用：杨恬, 田代印. 囊性纤维化表型变异与修饰基因关系的研究进展[J]. 临床医学进展, 2024, 14(5): 524-529. https://doi.org/10.12677/acm.2024.1451458

参考文献

[1] Butnariu, L.I., Tarca, E., Cojocaru, E., et al. (2021) Genetic Modifying Factors of Cystic Fibrosis Phenotype: A Challenge for Modern Medicine. Journal of Clinical Medicine, 10, Article 5821. [Google Scholar] [CrossRef] [PubMed]
[2] Guo, X., Liu, K., Liu, Y., et al. (2018) Clinical and Genetic Characteristics of Cystic Fibrosis in CHINESE Patients: A Systemic Review of Reported Cases. Orphanet Journal of Rare Diseases, 13, Article No. 224. [Google Scholar] [CrossRef] [PubMed]
[3] Burke, W., Aitken, M.L., Chen, S.H., et al. (1992) Variable Severity of Pulmonary Disease in Adults with Identical Cystic Fibrosis Mutations. Chest, 102, 506-509. [Google Scholar] [CrossRef] [PubMed]
[4] Mckone, E.F., Emerson, S.S., Edwards, K.L., et al. (2003) Effect of Genotype on Phenotype and Mortality in Cystic Fibrosis: A Retrospective Cohort Study. The Lancet, 361, 1671-1676. [Google Scholar] [CrossRef] 
[5] Blackman, S.M., Deering-Brose, R., Mcwilliams, R., et al. (2006) Relative Contribution of Genetic and Nongenetic Modifiers to Intestinal Obstruction in Cystic Fibrosis. Gastroenterology, 131, 1030-1039. [Google Scholar] [CrossRef] [PubMed]
[6] Sepahzad, A., Morris-Rosendahl, D.J. and Davies, J.C. (2021) Cystic Fibrosis Lung Disease Modifiers and Their Relevance in the New Era of Precision Medicine. Genes, 12, Article 562. [Google Scholar] [CrossRef] [PubMed]
[7] Buranawuti, K., Boyle, M.P., Cheng, S., et al. (2007) Variants in Mannose-Binding Lectin and Tumour Necrosis Factor Alpha Affect Survival in Cystic Fibrosis. Journal of Medical Genetics, 44, 209-214. [Google Scholar] [CrossRef] [PubMed]
[8] Strug, L.J., Gonska, T., He, G., et al. (2016) Cystic Fibrosis Gene Modifier SLC26A9 Modulates Airway Response to CFTR-Directed Therapeutics. Human Molecular Genetics, 25, 4590-4600. [Google Scholar] [CrossRef] [PubMed]
[9] 林霖, 王岩, 吴传斌, 等. 囊性纤维化及其治疗方法的研究进展[J]. 药学学报, 2022, 57(7): 2024-2031.
[10] Gibson, R.L., Burns, J.L. and Ramsey, B.W. (2003) Pathophysiology and Management of Pulmonary Infections in Cystic Fibrosis. American Journal of Respiratory and Critical Care Medicine, 168, 918-951. [Google Scholar] [CrossRef] 
[11] Stahl, M., Steinke, E. and Mall, M.A. (2021) Quantification of Phenotypic Variability of Lung Disease in Children with Cystic Fibrosis. Genes, 12, Article 803. [Google Scholar] [CrossRef] [PubMed]
[12] Shen, Y., Liu, J., Zhong, L., et al. (2016) Clinical Phenotypes and Genotypic Spectrum of Cystic Fibrosis in Chinese Children. The Journal of Pediatrics, 171, 269-76. e1. [Google Scholar] [CrossRef] [PubMed]
[13] Cutting, G.R. (2015) Cystic Fibrosis Genetics: From Molecular Understanding to Clinical Application. Nature Reviews Genetics, 16, 45-56. [Google Scholar] [CrossRef] [PubMed]
[14] O’neal, W.K. and Knowles, M.R. (2018) Cystic Fibrosis Disease Modifiers: Complex Genetics Defines the Phenotypic Diversity in a Monogenic Disease. Annual Review of Genomics and Human Genetics, 19, 201-222. [Google Scholar] [CrossRef] [PubMed]
[15] Santis, G., Osborne, L., Knight, R.A., et al. (1990) Independent Genetic Determinants of Pancreatic and Pulmonary Status in Cystic Fibrosis. The Lancet, 336, 1081-1084. [Google Scholar] [CrossRef] 
[16] Rowntree, R.K. and Harris, A. (2003) The Phenotypic Consequences of CFTR Mutations. Annals of Human Genetics, 67, 471-485. [Google Scholar] [CrossRef] [PubMed]
[17] Mésinèle, J., Ruffin, M., Guillot, L., et al. (2022) Modifier Factors of Cystic Fibrosis Phenotypes: A Focus on Modifier Genes. International Journal of Molecular Sciences, 23, Article 14205. [Google Scholar] [CrossRef] [PubMed]
[18] Marson, F.A.L. (2018) Disease-Modifying Genetic Factors in Cystic Fibrosis. Current Opinion in Pulmonary Medicine, 24, 296-308. [Google Scholar] [CrossRef] 
[19] (2000) Erratum: EUROGAPPP PROJECT 1999-2000 Public and Professional Policy Committee (PPPC)* Population Genetic Screening Programmes: Proposed Recommendations of the European Society of Human Genetics. European Journal of Human Genetics, 8, 998-1000. [Google Scholar] [CrossRef] [PubMed]
[20] Cutting, G.R. (2006) Causes of Variation in the Cystic Fibrosis Phenotype. Annales Nestlé (English Ed.), 64, 111-117. [Google Scholar] [CrossRef] 
[21] Barrio, R. (2015) Management of Endocrine Disease: Cystic Fibrosis-Related Diabetes: Novel Pathogenic Insights Opening New Therapeutic Avenues. European Journal of Endocrinology, 172, R131-R141. [Google Scholar] [CrossRef] 
[22] Vanscoy, L.L., Blackman, S.M., Collaco, J.M., et al. (2007) Heritability of Lung Disease Severity in Cystic Fibrosis. American Journal of Respiratory and Critical Care Medicine, 175, 1036-1043. [Google Scholar] [CrossRef] 
[23] Flamant, C., Henrion-Caude, A., Boëlle, P.Y., et al. (2004) Glutathione-S-Transferase M1, M3, P1 and T1 Polymorphisms and Severity of Lung Disease in Children with Cystic Fibrosis. Pharmacogenetics, 14, 295-301. [Google Scholar] [CrossRef] [PubMed]
[24] Feuillet-Fieux, M.N., Nguyen-Khoa, T., Loriot, M.A., et al. (2009) Glutathione S-Transferases Related to P. aeruginosa Lung Infection in Cystic Fibrosis Children: Preliminary Study. Clinical Biochemistry, 42, 57-63. [Google Scholar] [CrossRef] [PubMed]
[25] Drumm, M.L., Konstan, M.W., Schluchter, M.D., et al. (2005) Genetic Modifiers of Lung Disease in Cystic Fibrosis. The New England Journal of Medicine, 353, 1443-1453. [Google Scholar] [CrossRef] 
[26] Arkwright, P.D., Laurie, S., Super, M., et al. (2000) TGF-β1 Genotype and Accelerated Decline in Lung Function of Patients with Cystic Fibrosis. Thorax, 55, 459-462. [Google Scholar] [CrossRef] [PubMed]
[27] Trojan, T., Alejandre Alcazar, M.A., Fink, G., et al. (2022) The Effect of TGF-β(1) Polymorphisms on Pulmonary Disease Progression in Patients with Cystic Fibrosis. BMC Pulmonary Medicine, 22, Article No. 183. [Google Scholar] [CrossRef] [PubMed]
[28] Collaco, J.M., Vanscoy, L., Bremer, L., et al. (2008) Interactions between Secondhand Smoke and Genes That Affect Cystic Fibrosis Lung Disease. JAMA, 299, 417-424. [Google Scholar] [CrossRef] [PubMed]
[29] Nourkami-Tutdibi, N., Freitag, K., Zemlin, M., et al. (2021) Genetic Association with Pseudomonas aeruginosa Acquisition in Cystic Fibrosis: Influence of Surfactant Protein D and Mannose-Binding Lectin. Frontiers in Immunology, 12, Article 587313. [Google Scholar] [CrossRef] [PubMed]
[30] Turner, M.W. (2003) The Role of Mannose-Binding Lectin in Health and Disease. Molecular Immunology, 40, 423-429. [Google Scholar] [CrossRef] 
[31] Chalmers, J.D., Fleming, G.B., Hill, A.T., et al. (2011) Impact of Mannose-Binding Lectin Insufficiency on the Course of Cystic Fibrosis: A Review and Meta-Analysis. Glycobiology, 21, 271-282. [Google Scholar] [CrossRef] [PubMed]
[32] Pinto, M.C., Quaresma, M.C., Silva, I.A.L., et al. (2021) Synergy in Cystic Fibrosis Therapies: Targeting SLC26A9. International Journal of Molecular Sciences, 22, Article 13064. [Google Scholar] [CrossRef] [PubMed]
[33] Gorrieri, G., Zara, F. and Scudieri, P. (2022) SLC26A9 as a Potential Modifier and Therapeutic Target in Cystic Fibrosis Lung Disease. Biomolecules, 12, Article 202. [Google Scholar] [CrossRef] [PubMed]
[34] Corvol, H., Mésinèle, J., Douksieh, I.H., et al. (2018) SLC26A9 Gene Is Associated with Lung Function Response to Ivacaftor in Patients with Cystic Fibrosis. Frontiers in Pharmacology, 9, Article 828. [Google Scholar] [CrossRef] [PubMed]
[35] De Paiva, A.C., Marson, F.A., Ribeiro, J.D., et al. (2014) Asthma: Gln27Glu and Arg16Gly Polymorphisms of the Beta2-Adrenergic Receptor Gene as Risk Factors. Allergy, Asthma & Clinical Immunology, 10, Article No. 8. [Google Scholar] [CrossRef] [PubMed]
[36] Hart, M.A., Konstan, M.W., Darrah, R.J., et al. (2005) Beta 2 Adrenergic Receptor Polymorphisms in Cystic Fibrosis. Pediatric Pulmonology, 39, 544-550. [Google Scholar] [CrossRef] [PubMed]
[37] Wright, F.A., Strug, L.J., Doshi, V.K., et al. (2011) Genome-Wide Association and Linkage Identify Modifier Loci of Lung Disease Severity in Cystic Fibrosis at 11p13 and 20q13.2. Nature Genetics, 43, 539-546. [Google Scholar] [CrossRef] [PubMed]
[38] Corvol, H., Blackman, S.M., Boëlle, P.Y., et al. (2015) Genome-Wide Association Meta-Analysis Identifies Five Modifier Loci of Lung Disease Severity in Cystic Fibrosis. Nature Communications, 6, Article No. 8382. [Google Scholar] [CrossRef] [PubMed]
[39] Zhou, Y.-H., Gallins, P.J., et al. (2023) Genetic Modifiers of Cystic Fibrosis Lung Disease Severity: Whole-Genome Analysis of 7,840 Patients. American Journal of Respiratory and Critical Care Medicine, 207, 1324-1333. [Google Scholar] [CrossRef] 

为你推荐