Association of polymorphism rs7903146 gene TCF7L2 with low concentrations of autoantibodies in latent autoimmune diabetes of adults (LADA)
https://doi.org/10.14341/DM2003418-21
Abstract
Aim. To determine the frequencies of alleles and genotypes of polymorphic marker rs7903146 of the TCF7L2 gene in latent autoimmune diabetes in adults (LADA) and healthy individuals. The aims of the study were also to compare the distribution of alleles and genotypes and to explore the association with the development of LADA.
Materials and methods. A total of 96 patients (46 females and 50 males) with LADA and 201 healthy individuals were examined. A quantitative determination of autoantibodies GADA, ICA, IA-2A and ZnT8 in the serum of LADA patients was performed. All patients underwent genotyping of rs7903146 of the TCF7L2 genes.
Results. There was an increased frequency of the T allele and genotype T+ of marker rs7903146 of the TCF7L2 gene in patients with LADA with low concentrations of autoantibodies compared to a group of patients with high concentrations and with controls. We observed significant associations of the T allele and genotype T+ with LADA in patients with low concentrations of autoantibodies [p = 0.02; odds ratio (OR) = 1.85; 95% confidence interval (CI) = 1.10–3.13 and p = 0.04; OR = 2.14; 95% CI = 1.01–4.53 for the T allele and genotype T+, respectively).
Conclusion. The results of the study suggest that LADA patients with low concentrations of autoantibodies have a genetically pre-determined similarity with patients with type 2 diabetes.
About the Authors
Iuliia V. SilkoRussian Federation
MD
Competing Interests:
No conflict of interest
Tatiana V. Nikonova
Russian Federation
MD, PhD
Competing Interests:
No conflict of interest
Olga N. Ivanova
Russian Federation
PhD
Competing Interests:
No conflict of interest
Svetlana M. Stepanova
Russian Federation
MD
Competing Interests:
No conflict of interest
Marina V. Shestakova
Russian Federation
MD, PhD, Professor
Competing Interests:
No conflict of interest
Ivan I. Dedov
Russian Federation
MD, PhD, Professor
Competing Interests:
No conflict of interest
References
1. Leslie RD, Palmer J, Schloot NC, Lernmark A. Diabetes at the crossroads: relevance of disease classification to pathophysiology and treatment. Diabetologia. 2016;59(1):13-20. doi: 10.1007/s00125-015-3789-z
2. Tuomi T, Santoro N, Caprio S, et al. The many faces of diabetes: a disease with increasing heterogeneity. The Lancet. 2014;383(9922):1084-1094. doi: 10.1016/s0140-6736(13)62219-9
3. Grant SF, Hakonarson H, Schwartz S. Can the genetics of type 1 and type 2 diabetes shed light on the genetics of latent autoimmune diabetes in adults? Endocr Rev. 2010;31(2):183-193. doi: 10.1210/er.2009-0029
4. Wagner R, Staiger H, Ullrich S, et al. Untangling the interplay of genetic and metabolic influences on beta-cell function: Examples of potential therapeutic implications involving TCF7L2 and FFAR1.Molecular Metabolism. 2014;3(3):261-267. doi: http://dx.doi.org/10.1016/j.molmet.2014.01.001
5. Tong Y, Lin Y, Zhang Y, et al. Association between TCF7L2gene polymorphisms and susceptibility to Type 2 Diabetes Mellitus: a large Human Genome Epidemiology (HuGE) review and meta-analysis.BMC Medical Genetics. 2009;10(1). doi: 10.1186/1471-2350-10-15
6. Assmann TS, Duarte GC, Rheinheimer J, et al. The TCF7L2 rs7903146 (C/T) polymorphism is associated with risk to type 2 diabetes mellitus in Southern-Brazil. Arq Bras Endocrinol Metabol.2014;58(9):918-925. doi: 10.1590/0004-2730000003510
7. Wang J, Zhang J, Li L, et al. Association of rs12255372 in the TCF7L2 gene with type 2 diabetes mellitus: a meta-analysis. Brazilian Journal of Medical and Biological Research. 2013;46(4):382-393. doi: 10.1590/1414-431x20132677
8. Raj SM, Howson JM, Walker NM, et al. No association of multiple type 2 diabetes loci with type 1 diabetes. Diabetologia. 2009;52(10):2109-2116. doi: 10.1007/s00125-009-1391-y
9. Basile KJ, Guy VC, Schwartz S, Grant SF. Overlap of genetic susceptibility to type 1 diabetes, type 2 diabetes, and latent autoimmune diabetes in adults. Curr Diab Rep. 2014;14(11):550. doi: 10.1007/s11892-014-0550-9
10. Cervin C, Lyssenko V, Bakhtadze E, et al. Genetic similarities between latent autoimmune diabetes in adults, type 1 diabetes, and type 2 diabetes. Diabetes. 2008;57(5):1433-1437. doi: 10.2337/db07-0299
11. Lukacs K, Hosszufalusi N, Dinya E, et al. The type 2 diabetes-associated variant in TCF7L2 is associated with latent autoimmune diabetes in adult Europeans and the gene effect is modified by obesity: a meta-analysis and an individual study. Diabetologia. 2012;55(3):689-693. doi: 10.1007/s00125-011-2378-z
12. Szepietowska B, Moczulski D, Wawrusiewicz-Kurylonek N, et al. Transcription factor 7-like 2-gene polymorphism is related to fasting C peptide in latent autoimmune diabetes in adults (LADA). Acta Diabetol. 2010;47(1):83-86. doi: 10.1007/s00592-009-0133-4
13. Zampetti S, Spoletini M, Petrone A, et al. Association of TCF7L2 gene variants with low GAD autoantibody titre in LADA subjects (NIRAD Study 5). Diabet Med. 2010;27(6):701-704. doi: 10.1111/j.1464-5491.2010.02997.x
14. Bakhtadze E, Cervin C, Lindholm E, et al. Common variants in the TCF7L2 gene help to differentiate autoimmune from non-autoimmune diabetes in young (15-34 years) but not in middle-aged (40-59 years) diabetic patients. Diabetologia. 2008;51(12):2224-2232. doi: 10.1007/s00125-008-1161-2
15. Pettersen E, Skorpen F, Kvaloy K, et al. Genetic heterogeneity in latent autoimmune diabetes is linked to various degrees of autoimmune activity: results from the Nord-Trondelag Health Study. Diabetes.2010;59(1):302-310. doi: 10.2337/db09-0923
16. Lohmann T, Kellner K, Verlohren HJ, et al. Titre and combination of ICA and autoantibodies to glutamic acid decarboxylase discriminate two clinically distinct types of latent autoimmune diabetes in adults (LADA). Diabetologia. 2001;44(8):1005-1010. doi: 10.1007/s001250100602
17. Rosário PWS, Reis JS, Fagundes TA, et al. Latent autoimmune diabetes in adults (LADA): usefulness of anti-GAD antibody titers and benefit of early insulinization. ArqBras Endocrinol Metabol.2007;51(1):52-58. doi: 10.1590/s0004-27302007000100009
18. Калькулятор для расчета статистики в исследованиях «случай-контроль». [Kal’kulyator dlya rascheta statistiki v issledovaniyakh «sluchay-kontrol’». (in Russ)]. Available from: http://gen-exp.ru/ calculator_or.php.
19. Laugesen E, Ostergaard JA, Leslie RD, et al. Latent autoimmune diabetes of the adult: current knowledge and uncertainty. Diabet Med. 2015;32(7):843-852. doi: 10.1111/dme.12700
20. Дедов И.И., Шестакова М.В., Кураева Т.Л., и др. Нозологическая гетерогенность, молекулярная генетика и иммунология аутоиммунного сахарного диабета. // Вестник РАМН. – 2015. – Т. 70. - №2 – С. 132-138. [Dedov II, Shestakova MV, Kuraeva TL, et al. Nozological Heterogeneity, Molecular Genetics and Immunology of Autoimmune Diabetes Mellitus. Annals of the Russian academy of medical sciences. 2015;70(2):132-138. (in Russ)].
21. Никонова Т.В., Апанович П.В., Пекарева Е.В., и др. Иммуногенетические аспекты медленно прогрессирующего аутоимунного диабета у взрослых (LADA) // Сахарный диабет. - 2011. - Т. 14. - №1 - C. 28-34. [Nikonova TV, Apanovich PV, Pekareva EV, Gorelysheva VA, Stepanova SM, Tishina YV, et al. Immunogenetic characteristics of LADA. Diabetes mellitus. 2011;14(1):28-34. (in Russ)]. doi: 10.14341/2072-0351-6247
22. Redondo MJ, Muniz J, Rodriguez LM, et al. Association of TCF7L2 variation with single islet autoantibody expression in children with type 1 diabetes. BMJ Open Diabetes Res Care. 2014;2(1):e000008. doi: 10.1136/bmjdrc-2013-000008
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For citations:
Silko I.V., Nikonova T.V., Ivanova O.N., Stepanova S.M., Shestakova M.V., Dedov I.I. Association of polymorphism rs7903146 gene TCF7L2 with low concentrations of autoantibodies in latent autoimmune diabetes of adults (LADA). Diabetes mellitus. 2016;19(3):199-203. (In Russ.) https://doi.org/10.14341/DM2003418-21

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