Моногенний діабет в Україні: гени, фенотип, лікування
DOI:
https://doi.org/10.24026/1818-1384.3(59).2017.110893Ключові слова:
MODY, моногенний діабет, сульфонілсечовина, лікування, УкраїнаАнотація
Актуальність проблеми. Діабет дорослого типу у молодих (MODY) раніше не вивчався в Україні. Ми дослідили генетичну етіологію у вибраній когорті пацієнтів з цукровим діабетом (ЦД), вік яких на момент діагностування ЦД був від 9 місяців до 25 років, а також у членів їх сімей. Матеріали та методи. Генетичне тестування найбільш поширених генів MODY (GCK, HNF1A, HNF4A, HNF1B та INS) було здійснено для 48 сімей (51 хворий) за допомогою Sanger секвенування або таргетного секвенування наступного покоління (tNGS). Результати. Генетичний діагноз MODY було підтверджено у 24/51 хворих з 21/48 сімей (44%). HNF1A та HNF4A MODY були найбільш поширеними варіантами та склали 11/24 випадків MODY (46%). Десять пацієнтів з HNF1A/HNF4A та ABCC8 MODY та незадовільним глікемічним контролем були успішно переведені на препарати сульфонілсечовини. Середній рівень HbA1c знизився з 7,9% [7,5-8,4] до 6,3% [5,9-6,7] через 3 місяці після переводу (р=0,0001). Висновки. Генетичне тестування виявило, що у пацієнтів з MODY в Україні найчастішими були мутації в гені HNF1A/HNF4A. Перехід на препарати сульфонілсечовини суттєво покращив глікемічний контроль цих пацієнтів.Посилання
Zelinska NB, Rudenko NG. [Statistics of pediatric endocrinology in Ukraine: summary of 2016]. Ukrainskyi zhurnal dytiachoi endokrynolohii. 2017; (2): 5-17. [Ukrainian].
Globa E, Zelinska N, Mackay D, Temple K, Houghton J, Hattersley AT, Flanagan SE and Ellard S. Neonatal diabetes in Ukraine: incidence, genetics, clinical phenotype and treatment. J Pediatr Endocrinol Metab. 2015; 28 (11-12): 1279-1286. https://doi.org/10.1515/jpem-2015-0170
Lebl J, Pruhova S, Dusatkova P, et al. Does continuous targeted medical education increase the rate of referrals for genetic testing for MODY? The Czech experience. Pediatric Diabetes. 2012; 13 (S.17): 32. https://doi.org/10.1111/j.1399-5448.2012.00918.x
Fendler W, Borowiec M, Baranowska-Zazwiecka A, et al. Prevalence of monogenic diabetes amongst Polish children after a nationwide genetic screening campaign. Diabetologia. 2012; 55: 2631-2635. https://doi.org/10.1007/s00125-012-2621-2
Frayling TM, Evans JC, Bulman MP, et al. Beta-cell genes and diabetes: molecular and clinical characterization of mutations in transcription factors. Diabetes. 2001;50 (Suppl 1): S94-S100. https://doi.org/10.2337/diabetes.50.2007.s94
Lenderman H. Is maturity onset diabetes at young age (MODY) more common in Europe than previously assumed? Lancet. 1995; 345: 648. https://doi.org/10.1016/s0140-6736(95)90548-0
Shields BM, Hicks S, Shepherd MH, Colclough K, Hattersley AT, Ellard S. Maturity-onset diabetes of the young (MODY): how many cases are we missing? Diabetologia. 2010; 53: 2504-2508. https://doi.org/10.1007/s00125-010-1799-4
Shields BM, McDonald TJ, Ellard S, Campbell MJ, Hyde C, Hattersley AT. The development and validation of a clinical prediction model to determine the probability of MODY in patients with young-onset diabetes. Diabetologia. 2012; 55(5): 1265-1272. https://doi.org/10.1007/s00125-011-2418-8
Pearson E, Starkey BJ, Powell RJ, Gribble F, Clark PM, Hattersley AT. Genetic cause of hyperglycaemia and response to treatment in diabetes. Lancet. 2003 Oct 18; 362(9392): 1275-1281. https://doi.org/10.1016/s0140-6736(03)14571-0
Ellard S, Bellanné-Chantelot C, Hattersley A. Best practice guidelines for the molecular genetic diagnosis of maturity-onset diabetes of the young. Diabetologia. 2008 Apr; 51(4): 546-553. https://doi.org/10.1007/s00125-008-0942-y
IDF/ISPAD 2011 Global Guideline for diabetes in childhood and adolescence. [Internet]. Available from: https://www.ispad.org/?page=IDFISPAD2011
Winter W, Nakamura M, House D. Monogenic diabetes mellitus in youth. The MODY syndromes. Endocrinol Metab Clin North Am. 1999; 28(4): 765-785. https://doi.org/10.1016/s0889-8529(05)70101-8
Edghill E, Minton J, Groves C, et al. Sequencing of candidate genes selected by beta cell experts in Monogenic Diabetes of unknown aetiology. J Pancreas (Online). 2010; 11(1): 14-17.
Naylor R, Greeley SAW, Bell G, Philipson L. Genetics and pathophysiology of neonatal diabetes mellitus. J Diabetes Investig. 2011; 2(3): 158-169. https://doi.org/10.1111/j.2040-1124.2011.00106.x
Cockburn BN, Bermano G, Boodram LL, et al. Insulin promoter factor-1 mutations and diabetes in Trinidad: identification of a novel diabetes-associated mutation (E224K) in an Indo-Trinidadian family. J Clin Endocrinol Metab. 2004; 89: 971-978. https://doi.org/10.1210/jc.2003-031282
Stoffers D, Ferrer J, Clarke W, Habener J. Early-onset type-ll diabetes mellitus (MODY4) linked to IPF1. Nat Genet. 1997; 17: 138-139. https://doi.org/10.1038/ng1097-138
Kristinsson SY, Thorolfsdottir ET, Talseth B, et al. MODY in Iceland is associated with mutations in HNF-1alpha and a novel mutation in NeuroD1. Diabetologia. 2001; 44: 2098-2103. https://doi.org/10.1007/s001250100016
Malecki MT, Jhala U, Antonellis A, et al. Mutations in NEUROD1 are associated with the development of type 2 diabetes mellitus. Nat Genet. 1999; 23: 323-328. https://doi.org/10.1038/15500
Raeder H, Johansson S, Holm PI, et al. Mutations in the CEL VNTR cause a syndrome of diabetes and pancreatic exocrine dysfunction. Nat Genet. 2006; 38: 54-62. https://doi.org/10.1038/ng1708
Dusatkova L, Dusatkova P, Vosahlo J, Vesela K, Cinek O, Lebl J, Pruhova S. Frameshift mutations in the insulin gene leading to prolonged molecule of insulin in two families with Maturity-Onset Diabetes of the Young. European Journal of Medical Genetics. 2015; 58: 230-234. https://doi.org/10.1016/j.ejmg.2015.02.004
Gardner D, Tai E. Clinical features and treatment of maturity onset diabetes of the young (MODY). Diabetes Metab Syndr Obes. 2012; 5: 101-108. https://doi.org/10.2147/dmso.s23353
Barrio R, Bellanné-Chantelot C, Moreno J. Nine novel mutations in maturity-onset diabetes of the young (MODY) candidate genes in 22 Spanish families. J Clin Endocrinol Metab. 2002; 87(6): 2532-2539. https://doi.org/10.1210/jcem.87.6.8530
Borowiec M, Antosik K, Fendler W, Deja G, Jarosz-Chobot P, et al. Specific clinical pattern for glucokinase gene mutations in MODY families. Pediatric Diabetes. 2010; 11 (S.14): 31.
Colclough K, Bellanne-Chantelot C, Saint-Martin C, Flanagan S, Ellard S. Mutations in the genes encoding the transcription factors Hepatocyte Nuclear Factor 1 alpha (HNF1A) and 4 alpha (HNF4A) in Maturity-Onset Diabetes of the Young (MODY) and hyperinsulinaemic hypoglycaemia. Hum Mutat. 2013; 34(5): 669-685. https://doi.org/10.1002/humu.22279
Heiervang E, Følling I, Søvik O, et al. Maturity-onset diabetes of the young. Studies in a Norwegian family. Acta Paediatr Scand. 1989; 78(1): 74-80. https://doi.org/10.1111/j.1651-2227.1989.tb10890.x
Sovik O, Njolstad P, Folling I, Sagen J, Cockburn B, Bell G. Hyperexcitability to sulphonylurea in MODY3. Diabetologia. 1998; 41(5): 607-608. https://doi.org/10.1007/s001250050956
Pearson E, Liddell W, Shepherd M, Corrall R, Hattersley A. Sensitivity to sulphonylureas in patients with hepatocyte nuclear factor-1alpha gene mutations: evidence for pharmacogenetics in diabetes. Diabet Med. 2000; 17(7): 543-545. https://doi.org/10.1046/j.1464-5491.2000.00305.x
Timsit J, Bellanné-Chantelot C, Dubois-Laforgue D, Velho G. Diagnosis and management of maturity-onset diabetes of the young. Treat Endocrinol. 2005; 4(1): 9-18. https://doi.org/10.2165/00024677-200504010-00002
Isomaa B, Henricsson M, Lehto M, et al. Chronic diabetic complications in patients with MODY3 diabetes. Diabetologia. 1998; 41(4): 467-473. https://doi.org/10.1007/s001250050931
Steele A, Shields B, Shepherd M, Ellard S, Hattersley A, Pearson E. Increased all-cause and cardiovascular mortality in monogenic diabetes as a result of mutations in the HNF1A gene. Diabet Med. 2010; 27(2): 157-161. https://doi.org/10.1111/j.1464-5491.2009.02913.x
Pearson E, Pruhova S, Tack C, et al. Molecular genetics and phenotypic characteristics of MODY caused by hepatocyte nuclear factor 4 alpha mutations in a large European collection. Diabetologia. 2005; 48(5): 878-885. https://doi.org/10.1007/s00125-005-1738-y
Fajans S, Brown M. Administration of sulfonylureas can increase glucose-induced insulin secretion for decades in patients with maturity-onset diabetes of the young. Diabetes Care. 1993; 16(9): 1254-1261. https://doi.org/10.2337/diacare.16.9.1254
Iwasaki N, Ogata M, Tomonaga O, et al. Liver and kidney function in Japanese patients with maturity-onset diabetes of the young. Diabetes Care. 1998; 21(12): 2144-2148. https://doi.org/10.2337/diacare.21.12.2144
Montoli A, Colussi G, Massa O, et al. Renal cysts and diabetes syndrome linked to mutations of the hepatocyte nuclear factor-1 beta gene: description of a new family with associated liver involvement. Am J Kidney Dis. 2002; 40(2): 397-402. https://doi.org/10.1053/ajkd.2002.34538
Bellanné-Chantelot C, Chauveau D, Gautier J, et al. Clinical spectrum associated with hepatocyte nuclear factor-1beta mutations. Ann Intern Med. 2004; 6140(7): S. 510-517. https://doi.org/10.7326/0003-4819-140-7-200404060-00009
Besser R, Shepherd M, McDonald T, et al. Urinary C-Peptide creatinine ratio is a practical outpatient tool for identifying Hepatocyte Nuclear Factor 1-α/Hepatocyte Nuclear Factor 4-α Maturity-Onset Diabetes of the Young from long-duration type 1 diabetes. Diabetes Care. 2011; 34(2): 286-291. https://doi.org/10.2337/dc10-1293
Stanik J, Dusatkova P, Cinek O, Valentinova L, Huckova M, et al. De novo mutations of GCK, HNF1A and HNF4A may be more frequent in MODY than previously assumed. Diabetologia. 2014; 57: 480-484. https://doi.org/10.1007/s00125-013-3119-2
Ellard S, Lango Allen H, De Franco E, Flanagan S, et al. Improved genetic testing for monogenic diabetes using targeted next-generation sequencing. Diabetologia 2013; 56: 1958-1963. https://doi.org/10.1007/s00125-013-2962-5
Haliloglu B, Hysenaj G, Atay Z, Guran T, Abalı S, et al. GCK gene mutations are a common cause of childhood-onset MODY (maturity-onset diabetes of the young) in Turkey. Clinical Endocrinology. 2016; 85: 393-399. https://doi.org/10.1111/cen.13121
Almeida S, Garcia I, Barreda A, Munoz O, Nunez A, et al. Prevalence of GCK and HNF1A mutations in a cohort of Spanish children diagnosed with monogenic diabetes. Pediatric Diabetes. 2013; 14 (Suppl.18):133-134.
Schober E, Rami B, Grabert M, et al. Phenotypical aspects of maturity-onset diabetes of the young (MODY diabetes) in comparison with type 2 diabetes mellitus (T2DM) in children and adolescents: experience from a large multicentre database. Diabet Med J Br Diabet Assoc. 2009; 26: 466-473. https://doi.org/10.1111/j.1464-5491.2009.02720.x
Pihoker C, Gilliam LK, Ellard S, Dabelea D, Davis C, et al. Prevalence, Characteristics and Clinical Diagnosis of Maturity Onset Diabetes of the Young Due to Mutations in HNF1A, HNF4A, and Glucokinase: Results from the SEARCH for Diabetes in Youth. J Clin Endocrinol Metab. 2013; 8(10): 4055-4062. https://doi.org/10.1210/jc.2013-1279
##submission.downloads##
Опубліковано
Номер
Розділ
Ліцензія
Ця робота ліцензується відповідно до Creative Commons Attribution-NonCommercial 4.0 International License.
