Association of rs7903146 TCF7L2, rs1042714 ADRB2 with the changes in body fat mass in different types of therapy of early carbohydrate metabolism disorders
https://doi.org/10.14341/omet12807
Abstract
BACKGROUND: Depending on the polymorphism of genes that that are involved in metabolism, the response of patients to different types of therapy may differ. Despite the potential effect of rs7903146 TCF7L2 and rs1042712 ADRB2 on changes in body composition in different types of therapy of early carbohydrate metabolism disorders, these associations haven’t been studied yet. AIM: To study the influence of rs7903146 TCF7L2, rs1042714 ADRB2 on changes in body fat composition in different types of therapy of early carbohydrate metabolism disorders.
MATERIALS AND METHODS: The study involved patients with overweight or obesity and risk factors for Type 2 Diabetes development. All patients underwent genotyping with the real-time polymerase chain reaction, oral glucose tolerance test and bioimpedancemetry. Further, the patients were divided into two groups. First group kept a diet with the exclusion of simple and limitation of complex carbohydrates and fats. Second group took metformin in addition to the diet. Three months after bioimpedancemetry was performed again.
RESULTS: The research involved 73 patients (the mean age 48±12 y.o., the mean BMI 34,27±6,18 kg/m2 ). The diet therapy group consisted of 47 people. Other 26 patients took metformin in addition to the diet. In group of diet, T allele carriers of rs7903146 TCF7L2 were characterized with more decrease in fat mass compared with CC homozygotes (- 7.90 ± 9.46% vs. -1.54 ± 8.98%, p = 0.027). CC genotype carriers of rs7903146 TCF7L2 in group of metformin and the diet had a tendency for more decrease in hip circumference compared with T allele carriers (-4.95 ± 3.34% vs. — 2.5 ± 2.96%, p = 0.064). Carriers of C allele in homozygous state of rs1042714 ADRB2, who took metformin with the diet, demonstrated more decrease in hip circumference (- 5.81 ± 3.00% vs. -2.50 ± 2.7%, p = 0.009), the tendency for decrease in fat mass (-8.28 ± 8.86% vs. — 3.20 ± 5.09%, p = 0.068) and waist circumference (-5.91 ± 4.29% vs. -3.03 ± 4.01 %, p = 0.091) compared with G allele carriers. The association of rs7903146 TCF7L2 and rs1042714 ADRB2 with changes in total body weight was not observed (p> 0.05).
CONCLUSION: Single nucleotide polymorphisms rs7903146 TCF7L2 and rs1042714 ADRB2 influence on body fat composition in patients with early carbohydrate metabolism disorders in various types of treatment.
About the Authors
F. V. ValeevaRussian Federation
Farida V. Valeeva, MD, PhD, Professor
Kаzan
Researcher ID: X-5363-2019;
eLibrary SPIN: 2082-3980
M. S. Medvedeva
Russian Federation
Mariya S. Medvedeva, MD
49 Butlerov str., 420012 Kаzan, Republic of Tatarstan
eLibrary SPIN: 3109-0333
T. A. Kiseleva
Russian Federation
Tat’yana A. Kiseleva, MD, PhD
Kаzan
Researcher ID: X-8889-2019;
eLibrary SPIN: 8159-0120
K. B. Khasanova
Russian Federation
Kamilya B. Khasanova, MD
Kаzan
Researcher ID: X-8667-2019;
eLibrary SPIN: 9494-9940
G. F. Gabidinova
Russian Federation
Gulnaz F. Gabidinova
Kаzan
eLibrary SPIN: 8893-2184
References
1. Dedov II, Shestakova MV, Mayorov AYu, et al. Standards of specialized diabetes care. Diabetes Mellitus. 2019;22(S1):1-144 (In Russ.). doi: https://doi.org/10.14341/DM221S1.
2. Zhou J, Massey S, Story D, Li L. Metformin: An Old Drug with New Applications. Int J Mol Sci. 2018;19(10):2863. doi: https://doi.org/10.3390/ijms19102863
3. Bankura B, Das M. Inter-patient Variability in Clinical Efficacy of Metformin in Type 2 Diabetes Mellitus Patients in West Bengal, India. J Metab Syndr. 2016;05(02). doi: https://doi.org/10.4172/2167-0943.1000198
4. Chen X, Ayala I, Shannon C, et al. The Diabetes Gene and Wnt Pathway Effector TCF7L2 Regulates Adipocyte Development and Function. Diabetes. 2018;67(4):554-568. doi: https://doi.org/10.2337/DB17-0318
5. Geoghegan G, Simcox J, Seldin MM, et al. Targeted deletion of Tcf7l2 in adipocytes promotes adipocyte hypertrophy and impaired glucose metabolism. Molecular metabolism. 2019;24:44-63. doi: https://doi.org/10.1016/J.MOLMET.2019.03.003
6. Yi F, Brubaker PL, Jin T. TCF-4 Mediates Cell Type-specific Regulation of Proglucagon Gene Expression by β-Catenin and Glycogen Synthase Kinase-3β. J Biol Chem. 2005;280(2):1457-1464. doi: https://doi.org/10.1074/jbc.M411487200
7. Zhou Y, Park SY, Su J, et al. TCF7L2 is a master regulator of insulin production and processing. Human molecular genetics. 2014;23(24):6419-6431. doi: https://doi.org/10.1093/HMG/DDU3598
8. Lou L, Wang J, Wang J. Genetic associations between Transcription Factor 7 like 2 rs7903146 polymorphism and type 2 diabetes mellitus: A meta-analysis of 115,809 subjects. Diabetol Metab Syndr. 2019;11(1):1-7. doi: https://doi.org/10.1186/s13098-019-0451-9
9. Del Bosque-Plata L, Martínez-Martínez E, Espinoza-Camacho MÁ, Gragnoli C. The Role of TCF7L2 in Type 2 Diabetes. Diabetes. 2021;70(6):1220-1228. doi: https://doi.org/10.2337/DB20-0573
10. Nikitin AG, Potapov VA, Brovkin AN, et al. Association of the polymorphisms of the tcf7l2 genes with type 2 diabetes. Journal of Clinical Practice. 2014;5(1):4-11. (In Russ.). doi: https://doi.org/10.17816/clinpract514-11
11. van der Kroef S, Noordam R, Deelen J, et al. Association between the rs7903146 Polymorphism in the TCF7L2 Gene and Parameters Derived with Continuous Glucose Monitoring in Individuals without Diabetes. PLoS One. 2016;11(2):e0149992. doi: https://doi.org/10.1371/journal.pone.0149992
12. Gupta V, Khadgawat R, Ng HKT, et al. Association of TCF7L2 and ADIPOQ with Body Mass Index, Waist–Hip Ratio, and Systolic Blood Pressure in an Endogamous Ethnic Group of India. Genet Test Mol Biomarkers. 2012;16(8):948-951. doi: https://doi.org/10.1089/gtmb.2012.0051
13. McCaffery JM, Jablonski KA, Franks PW, et al. TCF7L2 Polymorphism, Weight Loss and Proinsulin:Insulin Ratio in the Diabetes Prevention Program. PLoS One. 2011;6(7):e21518. doi: https://doi.org/10.1371/journal.pone.0021518
14. Li L, Wang J, Ping Z, et al. Interaction analysis of gene variants of TCF7L2 and body mass index and waist circumference on type 2 diabetes. Clin Nutr. 2020;39(1):192-197. doi: https://doi.org/10.1016/j.clnu.2019.01.014
15. Noordam R, Zwetsloot CPA, de Mutsert R, et al. Interrelationship of the rs7903146 TCF7L2 gene variant with measures of glucose metabolism and adiposity: The NEO study. Nutr Metab Cardiovasc Dis. 2018;28(2):150-157. doi: https://doi.org/10.1016/j.numecd.2017.10.012
16. Valeeva FV, Kiseleva TA, Khasanova KB, et al. Analysis of associations of polymorphous markers oftcf7l2 gene with diabetes mellitus of the 2nd type in the case of residents of the Republic of Tatarstan. Meditsinskii al’manakh. 2017;6(51):126-129. (In Russ.).
17. Bondar’ IA, Filipenko ML, Shabel’nikova OY, Sokolova EA. Rs7903146 variant of TCF7L2 gene and rs18012824 variant of PPARG2 gene (Pro12Ala) are associated with type 2 diabetes mellitus in Novosibirsk population. Diabetes mellitus. 2013;16(4):17-22. (In Russ.). doi: https://doi.org/10.14341/DM2013417-22
18. Brodde O-E. β1- and β2-Adrenoceptor polymorphisms and cardiovascular diseases. Fundam Clin Pharmacol. 2008;22(2):107-125. doi: https://doi.org/10.1111/j.1472-8206.2007.00557.x
19. Sarpeshkar V, Bentley DJ. Adrenergic-beta(2) receptor polymorphism and athletic performance. Journal of human genetics. 2010;55(8):479-485. doi: https://doi.org/10.1038/JHG.2010.42
20. Dahlman I, Arner P. Genetics of Adipose Tissue Biology. Progress in Molecular Biology and Translational Science. 2010;94:39-74. doi: https://doi.org/10.1016/B978-0-12-375003-7.00003-0
21. Jalba MS, Rhoads GG, Demissie K. Association of codon 16 and codon 27 beta 2-adrenergic receptor gene polymorphisms with obesity: a meta-analysis. Obesity (Silver Spring). 2008;16(9):2096-2106. doi: https://doi.org/10.1038/oby.2008.327
22. Zhang H, Wu J, Yu L. Association of Gln27Glu and Arg16Gly polymorphisms in Beta2-adrenergic receptor gene with obesity susceptibility: a meta-analysis. PloS One. 2014;9(6). doi: https://doi.org/10.1371/JOURNAL.PONE.0100489
23. Hsiao TJ, Lin E. Evaluation of the glutamine 27 glutamic acid polymorphism in the adrenoceptor β2 surface gene on obesity and metabolic phenotypes in Taiwan. J Investig Med. 2014;62(2):310-315. doi: https://doi.org/10.2310/JIM.0000000000000030
24. Prior SJ, Goldberg AP, Ryan AS. ADRB2 haplotype is associated with glucose tolerance and insulin sensitivity in obese postmenopausal women. Obesity. 2011;19(2):396-401. doi: https://doi.org/10.1038/OBY.2010.197
25. Shakhanova A, Aukenov N, Nurtazina A, et al. Association of polymorphism genes LPL, ADRB2, AGT and AGTR1 with risk of hyperinsulinism and insulin resistance in the Kazakh population. Biomedical reports. 2020;13(5):1-10. doi: https://doi.org/10.3892/BR.2020.1342
26. Saliba LF, Reis RS, Brownson RC, et al. Obesity-related gene ADRB2, ADRB3 and GHRL polymorphisms and the response to a weight loss diet intervention in adult women. Genetics and molecular biology. 2014;37(1):15-22. doi: https://doi.org/10.1590/S1415-47572014000100005
27. Ruiz JR, Larrante E, Margareto J, et al. Role of β₂-adrenergic receptor polymorphisms on body weight and body composition response to energy restriction in obese women: preliminary results. Obesity (Silver Spring). 2011;19(1):212-215. doi: https://doi.org/10.1038/OBY.2010.130
28. Szendrei B, González-Lamuño D, Amigo T, et al. Influence of ADRB2 Gln27Glu and ADRB3 Trp64Arg polymorphisms on body weight and body composition changes after a controlled weightloss intervention. Appl Physiol Nutr Metab. 2016;41(3):307-314. doi: https://doi.org/10.1139/apnm-2015-0425
29. Kravtsova OA. Struktura yadernogo genofonda povolzhskikh tatar (po dannym autosomnykh mikrosatellitnykh lokusov). Uchenye zapiski Kazanskogo universiteta. Seriya Estestvennye nauki. 2007;149(2):138-147 (In Russ.).
30. Roswall N, Ahluwalia TS, Romaguera D, et al. Association between Mediterranean and Nordic diet scores and changes in weight and waist circumference: influence of FTO and TCF7L2 loci 1-3. Am J Clin Nutr. 2014;100:1188-1197. doi: https://doi.org/10.3945/ajcn.114.089706
31. Dujic T, Bego T, Malenica M, et al. Effects of TCF7L2 rs7903146 variant on metformin response in patients with type 2 diabetes. Bosn J Basic Med Sci. 2019;19(4):368-374. doi: https://doi.org/10.17305/BJBMS.2019.4181
32. Gardner CD, Trepanowski JF, Gobbo LCD, et al. Effect of low-fat VS low-carbohydrate diet on 12-month weight loss in overweight adults and the association with genotype pattern or insulin secretion the DIETFITS randomized clinical trial. JAMA. 2018;319(7):667-679. doi: https://doi.org/10.1001/JAMA.2018.0245
33. Pawlyk AC, KM Giacomini KM, McKeon C, et al. Metformin pharmacogenomics: current status and future directions. Diabetes. 2014;63(8):2590-2599. doi: https://doi.org/10.2337/DB13-1367
Supplementary files
|
1. Figure 1. Association of rs7903146 TCF7L2 with changes in the proportion of body fat mass in group of diet therapy. | |
Subject | ||
Type | Исследовательские инструменты | |
View
(28KB)
|
Indexing metadata ▾ |
|
2. Figure 2. Association of rs7903146 TCF7L2 with changes in hip circumference in group of patients taking metformin in addition to diet therapy. | |
Subject | ||
Type | Исследовательские инструменты | |
View
(28KB)
|
Indexing metadata ▾ |
|
3. Figure 3. Association of rs1042714 ADRB2 with changes in hip circumference in group of taking metformin in addition to diet therapy. | |
Subject | ||
Type | Исследовательские инструменты | |
View
(28KB)
|
Indexing metadata ▾ |
|
4. Figure 4. Association of rs1042714 ADRB2 with changes in the proportion of body fat mass in group of patients taking metformin in addition to diet therapy. | |
Subject | ||
Type | Исследовательские инструменты | |
View
(29KB)
|
Indexing metadata ▾ |
|
5. Figure 5. Association of rs1042714 ADRB2 with changes in waist circumference in group of patients taking metformin in addition to diet therapy. | |
Subject | ||
Type | Исследовательские инструменты | |
View
(28KB)
|
Indexing metadata ▾ |
|
6. Figure 6. Association of rs1042714 ADRB2 genotype with changes in hip circumference in group of patients taking metformin in addition to diet therapy. | |
Subject | ||
Type | Исследовательские инструменты | |
View
(35KB)
|
Indexing metadata ▾ |
|
7. Figure 7. Association of rs1042714 ADRB2 with changes in the proportion of total body water in group of patients taking metformin in addition to diet therapy. | |
Subject | ||
Type | Исследовательские инструменты | |
View
(28KB)
|
Indexing metadata ▾ |
|
8. Figure 8. Association of rs1042714 ADRB2 with changes in the proportion of active cell mass in group of patients taking metformin in addition to diet therapy. | |
Subject | ||
Type | Исследовательские инструменты | |
View
(28KB)
|
Indexing metadata ▾ |
|
9. Figure 9. Association of rs1042714 ADRB2 genotype with changes in the proportion of active cell mass in group of patients taking metformin in addition to diet therapy. | |
Subject | ||
Type | Исследовательские инструменты | |
View
(38KB)
|
Indexing metadata ▾ |
Review
For citations:
Valeeva F.V., Medvedeva M.S., Kiseleva T.A., Khasanova K.B., Gabidinova G.F. Association of rs7903146 TCF7L2, rs1042714 ADRB2 with the changes in body fat mass in different types of therapy of early carbohydrate metabolism disorders. Obesity and metabolism. 2022;19(1):7-18. (In Russ.) https://doi.org/10.14341/omet12807

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0).