专题论文

从罕见内分泌疾病研究看精准内分泌学的发展

  • 冯时 ,
  • 刘爽 ,
  • 弓孟春 ,
  • 李梅 ,
  • 张抒扬
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  • 1. 中国医学科学院北京协和医院中心实验室, 北京 100730;
    2. 中国医学科学院北京协和医院心脏内科, 北京 100730
冯时,博士研究生,研究方向为临床医学及内分泌病学,电子信箱:joule_feng@163.com

收稿日期: 2017-05-26

  修回日期: 2017-07-31

  网络出版日期: 2017-08-26

基金资助

国家重点研发计划项目(2016YFC0901500);上海市出生缺陷防治重点实验室开放课题(16DZKF1007);国家卫生计生委2016年信息化与统计项目

Development of accurate endocrinology and the rare endocrine diseases

  • FENG Shi ,
  • LIU Shuang ,
  • GONG Mengchun ,
  • LI Mei ,
  • ZHANG Shuyang
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  • 1. Central Laboratories, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China;
    2. Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China

Received date: 2017-05-26

  Revised date: 2017-07-31

  Online published: 2017-08-26

摘要

罕见病指患病率低于7/10000的疾病,是精准医学研究的重要生物学模板和理想平台。多发性内分泌腺瘤综合征(MEN)、新生儿糖尿病、库欣氏综合征、先天性瘦素缺乏症等多种罕见内分泌疾病研究都反映了精准医学在内分泌领域的作用。在此基础上,本文进一步概括精准内分泌学的发展方向,在骨质疏松症、糖尿病、肥胖等内分泌疾病中应用精准医学,有助于对个体发病风险进行评估和预防,对复杂疾病进行精确诊断及分型,对疾病进行个体化治疗。此外,医学信息学在精准内分泌学领域的应用不仅可推动大数据平台建设,也提供了针对多因素复杂内分泌疾病的诊疗新思路。随着分子生物学技术的发展,建立罕见内分泌疾病的基因型和表型大数据平台,对于实现罕见内分泌疾病的精准诊疗具有重要意义。

本文引用格式

冯时 , 刘爽 , 弓孟春 , 李梅 , 张抒扬 . 从罕见内分泌疾病研究看精准内分泌学的发展[J]. 科技导报, 2017 , 35(16) : 52 -57 . DOI: 10.3981/j.issn.1000-7857.2017.16.007

Abstract

The rare diseases are characterized by an incidence less than 6.5/10000, which are both an ideal field of the precision medicine research and a significant area of clinical practice. The study of rare endocrine diseases, including the multiple endocrine neoplasia (MEN), the neonatal diabetes, the Cushing's syndrome and the congenital leptin deficiency syndrome, witnesses the development and the impact of the precision medicine. Based on a review in this respect, we discusses the future trend of the precision endocrinology in China. The precision medicine applied in the endocrine diseases such as the osteoporosis, the diabetes, and the obesity enables a better assessment of the individual risk of the endocrine diseases and can also help subclassify the diseases. Consequently, an individualized therapy could be realized. Furthermore, the medical informatics applied in the precision endocrinology may help the progress of building a big data platform and cast light in the new therapy of multifactorial diseases. The precision medicine of the rare endocrine diseases will become more prominant in a near future with the development of the sequencing technology and the establishment of the big data platform.

参考文献

[1] World Health Organization. Priority medicines for Europe and the world:A public health approach to innovation[EB/OL].[2017-06-20]. http://101.96.8.164/www.who.int/medicinedocs/documents/s16368e/s16368e.pdf.
[2] Valdez R, Grosse S D, Khoury M J. The need for a next-generation public health response to rare diseases[J]. Genetics in Medicine, 2016, 19:489-490.
[3] Trifonova O, Lokhov P, Archakov A. Postgenomics diagnostics:metabo-lomics approaches to human blood profiling[J]. Omics, 2013, 17(11):550-559.
[4] Klonoff D C. Precision medicine for managing diabetes[J]. Journal of Di-abetes Science and Technology, 2015, 9(1):3-7.
[5] Groop L. Genetics and neonatal diabetes:towards precision medicine[J]. Lancet, 2015, 386(9997):934-935.
[6] De Franco E, Flanagan S E, Houghton J A, et al. The effect of early, comprehensive genomic testing on clinical care in neonatal diabetes:an international cohort study[J]. Lancet, 2015, 386(9997):957-963.
[7] Bremond-Gignac D, Lewandowski E, Copin H. Contribution of electron-ic medical records to the management of rare diseases[J]. Biomed Re-search International, 2015, doi:10.1155/2015/954283.
[8] Moline J, Eng C. Multiple endocrine neoplasia type 2:an overview[J]. Genetics in Medicine, 2011, 13(9):755-764.
[9] Krampitz G W, Norton J A. RET gene mutations (genotype and pheno-type) of multiple endocrine neoplasia type 2 and familial medullary thy-roid carcinoma[J]. Cancer, 2014, 120(13):1920-1931.
[10] Kloos R T, Eng C, Evans D B, et al. Medullary thyroid cancer:Man-agement guidelines of the American Thyroid Association[J]. Thyroid, 2009, 19(6):565-612.
[11] Machens A. Early malignant progression of hereditary medullary thy-roid cancer[J]. New England Journal of Medicine, 2004, 350(9):943.
[12] Shepet K, Alhefdhi A, Lai N, et al. Hereditary medullary thyroid can-cer:age-appropriate thyroidectomy improves disease-free survival[J]. Annals of Surgical Oncology, 2013, 20(5):1451-1455.
[13] Cheng J B, Levine M A, Bell N H, et al. Genetic evidence that the hu-man CYP2R1 enzyme is a key vitamin D 25-hydroxylase[J]. PNAS, 2004, 101(20):7711-7715.
[14] Demir K, Kattan W E, Zou M, et al. Novel CYP27B1 gene mutations in patients with vitamin d-dependent rickets type 1A[J]. PLoS One, 2015, 10(7):e0131376.
[15] Hu W W, Ke Y H, He J W, et al. A novel compound mutation of CYP27B1 in a Chinese family with vitamin D-dependent rickets type 1A[J]. Journal of Pediatric Endocrinology and Metabolism, 2014, 27(3/4):335-341.
[16] Vaxillaire M, Froguel P. Monogenic diabetes:Implementation of trans-lational genomic research towards precision medicine[J]. Journal of Di-abetes, 2016, 8(6):782-795.
[17] Clayton R N, Raskauskiene D, Reulen R C, et al. Mortality and mor-bidity in Cushing's disease over 50 years in Stoke-on-Trent, UK:Au-dit and meta-analysis of literature[J]. The Journal of Clinical Endocri-nology and Metabolism, 2011, 96(3):632-642.
[18] Kaiser U B. Cushing's disease:Towards precision medicine[J]. Cell Re-search, 2015, 25(6):649-650.
[19] Wasim M, Awan F R, Najam S S, et al. Role of leptin deficiency, inef-ficiency, and leptin receptors in obesity[J]. Biochemical Genetics, 2016, 54(5):565-572.
[20] He J, Fang Y, Lin X, et al. The relationship between gene polymor-phism of leptin and leptin receptor and growth hormone deficiency[J]. Medical Science Monitor, 2016, 22:642-646.
[21] Paz-Filho G, Mastronardi C, Delibasi T, et al. Congenital leptin defi-ciency:Diagnosis and effects of leptin replacement therapy[J]. Arquiv-os Brasileiros de Endocrinologia e Metabologia, 2010, 54(8):690-697.
[22] Ahmadzadeh A, Ghods E, Mojarrad M, et al. Study on KAL1 gene mu-tations in idiopathic hypogonadotropic hypogonadism patients with xlinked recessive inheritance[J]. International Journal of Molecular and Cellular Medicine, 2015, 4(3):152-159.
[23] Razali N N, Hwu T T, Thilakavathy K. Phosphate homeostasis and ge-netic mutations of familial hypophosphatemic rickets[J]. Journal of Pe-diatric Endocrinology and Metabolism, 2015, 28(9/10):1009-1017.
[24] Thomas I H, DiMeglio L A. Advances in the classification and treat-ment of osteogenesis imperfecta[J]. Current Osteoporosis Reports, 2016, 14(1):1-9.
[25] Marshall C, Lopez J, Crookes L, et al. A novel homozygous variant in SERPINH1 associated with a severe, lethal presentation of osteogene-sis imperfecta with hydranencephaly[J]. Gene, 2016, 595(1):49-52.
[26] Marini J C, Reich A, Smith S M. Osteogenesis imperfecta due to muta-tions in non-collagenous genes:lessons in the biology of bone forma-tion[J]. Current Opinion in Pediatrics, 2014, 26(4):500-507.
[27] Laine C M, Joeng K S, Campeau P M, et al. WNT1 mutations in earlyonset osteoporosis and osteogenesis imperfecta[J]. New England Jour-nal of Medicine, 2013, 368(19):1809-1816.
[28] Vengerovskii A I, Khlusov I A, Nechaev K A. Molecular mechanisms of action of bisphosphonates and strontium ranelate[J]. Eksperimental-naia i Klinicheskaia Farmakologiia, 2014, 77(9):43-46.
[29] Sillero M A, de Diego A, Tavares J E, et al. Synthesis of ATP deriva-tives of compounds of the mevalonate pathway (isopentenyl di-and tri-phosphate; geranyl di-and triphosphate, farnesyl di-and triphosphate, and dimethylallyl diphosphate) catalyzed by T4 RNA ligase, T4 DNA ligase and other ligases Potential relationship with the effect of bisphosphonates on osteoclasts[J]. Biochemical Pharmacology, 2009, 78(4):335-343.
[30] Marozik P, Mosse I, Alekna V, et al. Association between polymor-phisms of VDR, COL1A1, and LCT genes and bone mineral density in Belarusian women with severe postmenopausal osteoporosis[J]. Me-dicina (Kaunas, Lithuania), 2013, 49(4):177.
[31] Ma M, Chen X, Lu L, et al. Identification of crucial genes related to postmenopausal osteoporosis using gene expression profiling[J]. Aging Clinical and Experimental Research, 2015, 28(6):1-8.
[32] Spegel P, Ekholm E, Tuomi T, et al. Metabolite profiling reveals nor-mal metabolic control in carriers of mutations in the glucokinase gene (MODY2)[J]. Diabetes, 2013, 62(2):653-661.
[33] Pawlyk A C, Giacomini K M, McKeon C, et al. Metformin pharmacoge-nomics:Current status and future directions[J]. Diabetes, 2014, 63(8):2590-2599.
[34] Kahn S E, Haffner S M, Heise M A, et al. Glycemic durability of rosi-glitazone, metformin, or glyburide monotherapy[J]. New England Jour-nal of Medicine, 2006, 355(23):2427-2443.
[35] Cook M N, Girman C J, Stein P P, et al. Initial monotherapy with ei-ther metformin or sulphonylureas often fails to achieve or maintain current glycaemic goals in patients with Type 2 diabetes in UK prima-ry care[J]. Diabetic Medicine, 2007, 24(4):350-358.
[36] Bailey C J, Turner R C. Metformin[J]. New England Journal of Medi-cine, 1996, 334(9):574-579.
[37] Group T S, Zeitler P, Hirst K, et al. A clinical trial to maintain glyce-mic control in youth with type 2 diabetes[J]. New England Journal of Medicine, 2012, 366(24):2247-2256.
[38] Morris A D, Boyle D I, MacAlpine R, et al. The diabetes audit and re-search in Tayside Scotland (DARTS) study:Electronic record linkage to create a diabetes register. DARTS/MEMO Collaboration[J]. British Medical Journal, 1997, 315(7107):524-528.
[39] Reitman M L, Schadt E E. Pharmacogenetics of metformin response:A step in the path toward personalized medicine[J]. Journal of Clinical Investment, 2007, 117(5):1226-1229.
[40] van Leeuwen N, Nijpels G, Becker M L, et al. A gene variant near ATM is significantly associated with metformin treatment response in type 2 diabetes:a replication and meta-analysis of five cohorts[J]. Dia-betologia, 2012, 55(7):1971-1977.
[41] Tkac I. Replication of the association of gene variant near ATM and response to metformin[J]. Pharmacogenomics, 2012, 13(12):1331-1332.
[42] Zhou K, Bellenguez C, Spencer C C, et al. Common variants near ATM are associated with glycemic response to metformin in type 2 di-abetes[J]. Nature Genetics, 2011, 43(2):117-120.
[43] Schnorr S L, Candela M, Rampelli S, et al. Gut microbiome of the Hadza hunter-gatherers[J]. Nature Communications, 2014, 5:3654.
[44] Li J, Jia H, Cai X, et al. An integrated catalog of reference genes in the human gut microbiome[J]. Nature Biotechnology, 2014, 32(8):834-841.
[45] Kolmeder C A, Salojarvi J, Ritari J, et al. Faecal metaproteomic analy-sis reveals a personalized and stable functional microbiome and limit-ed effects of a probiotic intervention in adults[J]. PLoS One, 2016, 11(4):e0153294.
[46] Sonnenburg J L, Backhed F. Diet-microbiota interactions as modera-tors of human metabolism[J]. Nature, 2016, 535(7610):56-64.
[47] Qin J, Li Y, Cai Z, et al. A metagenome-wide association study of gut microbiota in type 2 diabetes[J]. Nature, 2012, 490(7418):55-60.
[48] Turnbaugh P J, Ley R E, Mahowald M A, et al. An obesity-associated gut microbiome with increased capacity for energy harvest[J]. Nature, 2006, 444(7122):1027-1031.
[49] Liu W, Crott J W, Lyu L, et al. Diet-and genetically-induced obesity produces alterations in the microbiome, inflammation and wnt pathway in the intestine of Apc +/1638N mice:Comparisons and contrasts[J]. Journal of Cancer, 2016, 7(13):1780-1790.
[50] Marotz C A, Zarrinpar A. Treating obesity and metabolic syndrome with fecal microbiota transplantation[J]. The Yale Journal of Biology and Medicine, 2016, 89(3):383-388.
[51] Gulcher J, Stefansson K. Clinical risk factors, DNA variants, and the development of type 2 diabetes[J]. New England Journal of Medicine, 2009, 360(13):1360-1361.
[52] Cai L, Wu H, Li D, et al. Type 2 diabetes biomarkers of human gut microbiota selected via iterative sure independent screening method[J]. PLoS One, 2015, 10(10):e0140827.
[53] Vrieze A, Van Nood E, Holleman F, et al. Transfer of intestinal micro-biota from lean donors increases insulin sensitivity in individuals with metabolic syndrome[J]. Gastroenterology, 2012, 143(4):913-916
[54] Chambliss A B, Chan D W. Precision medicine:From pharmacogenom-ics to pharmacoproteomics[J]. Clinical Proteomics, 2016, 13(1):25.
[55] Chen P L, Shih S R, Wang PW, et al. Genetic determinants of antithy-roid drug-induced agranulocytosis by human leukocyte antigen geno-typing and genome-wide association study[J]. Nature Communications, 2015, 6:7633.
[56] Hallberg P, Eriksson N, Ibanez L, et al. Genetic variants associated with antithyroid drug-induced agranulocytosis:A genome-wide associ-ation study in a European population[J]. Lancet Diabetes Endocrinolo-gy, 2016, 4(6):507-516.
[57] 弓孟春, 王慧君, 卢宇蓝, 等. 药物基因组学临床部署的顶层设计[J]. 中国循证儿科杂志, 2016, 11(3):161-167. Gong Mengchun, Zou Wenhao, et al. Top design in clinical procedure of pharmacogenomics[J]. Chinese Journal of Evidence Based Pediat-rics, 2016, 11(3):198-206.
[58] Hawgood S, Hook-Barnard I G, O'Brien T C, et al. Precision medi-cine:Beyond the inflection point[J]. Science Translational Medicine, 2015, 7(300):300ps17.
[59] Li L, Cheng W Y, Glicksberg B S, et al. Identification of type 2 diabe-tes subgroups through topological analysis of patient similarity[J]. Sci-ence Translational Medicine, 2015, 7(311):311ra174.
[60] Bush W S, Oetjens M T, Crawford D C. Unravelling the human ge-nome-phenome relationship using phenome-wide association studies[J]. Nature Reviews Genetics, 2016, 17(3):129-145.
[61] Rastegar-Mojarad M, Ye Z, Kolesar JM, et al. Opportunities for drug repositioning from phenome-wide association studies[J]. Nature Bio-technology, 2015, 33(4):342-345.
[62] Eng C. Mendelian genetics of rare-and not so rare-cancers[J]. Annals of the New York Academy of Sciences, 2010, 1214(1):70-82.
[63] Turgeon J, Michaud V. Clinical decision support systems:Great prom-ises for better management of patients' drug therapy[J]. Expert Opin-ion on Drug Metabolism and Toxicology, 2016, 12(9):1-3.
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