The role of genetic factors in likelihood of type 2 diabetes mellitus
Е.S. Ageeva, Iu.I. Shramko, А.V. Kubyshkin, I.I. Fomochkina, А.А. Zhukova, C.О. Tarimov, S.G. Nastoyashchii, М.B. Zaurova
Crimea Federal University named after S.I. Georgievsky, 5/7 Lenina blvd, Simferopol, 295000, Russian Federation
Type 2 diabetes mellitus (DM2) is the ninth leading cause of worldwide mortality. To predict likelihood of the disease and its unfavorable clinical course with developing complications, it is necessary to consider genetic and molecular factors of DM2 pathogenesis. Therefore, the aim of this review was to analyze the role that belongs to genetic factors in molecular mechanisms of DM2 development and to establish the most significant single nucleotide polymorphisms (SNP) in DM2 pathogenesis.
The authors have analyzed literature sources found in such databases as CYBERLENINKA, E-library, and National Center for Biotechnology Information over the last 10 years as well as the integrated database GeneCards.
By now, Genome-Wide Association Studies (GWAS) have identified about 100 genes and more than 700 polymorphisms that influence DM2 risks and its likelihood. Classifications of candidate genes with their effects and expression being limited by external and internal transcription factors are rather tentative. Literature analysis has established certain ambiguousness of the role that belongs to genetic markers in DM2 pathogenesis. It is advisable to add new genetic markers of the PPARγ, TLR4, IRS and IL-6 genes to the existing test-systems. This will increase the likelihood of detecting hereditary predisposition to diabetes mellitus according to the key molecular-genetic mechanisms of its development and ensure implementation of relevant measures aimed at preventing the disease and early identification of genetic risk groups.
- Caruso R., Magon A., Baroni I., Dellafiore F., Arrigoni C., Pittella F., Ausili D. Health literacy in type 2 diabetes pa-tients: a systematic review of systematic reviews. Acta Diabetol., 2018, vol. 55, no. 1, pp. 1–12. DOI: 10.1007/s00592-017-1071-1
- Gruss S.M., Nhim K., Gregg E., Bell M., Luman E., Albright A. Public health approaches to Type 2 diabetes preven-tion: the US National Diabetes Prevention Program and Beyond. Curr. Diab. Rep., 2019, vol. 19, no. 9, pp. 78. DOI: 10.1007/s11892-019-1200-z
- Galicia-Garcia U., Benito-Vicente A., Jebari S., Larrea-Sebal A., Siddiqi H., Uribe K.B., Ostolaza H., Martín C. Pathophysiology of Type 2 Diabetes Mellitus. Int. J. Mol. Sci., 2020, vol. 21, no. 17, pp. 6275. DOI: 10.3390/ijms21176275
- Newgard C.B. Metabolomics and Metabolic Diseases: Where Do We Stand? Cell Metab., 2017, vol. 25, no. 1, pp. 43–56. DOI: 10.1016/j.cmet.2016.09.018
- Kiseleva T.A., Valeeva F.V., Islamova D.R., Medvedeva M.S. Genetic aspects of type 2 diabetes mellitus. Praktich-eskaya meditsina, 2023, vol. 21, no. 3, pp. 14–18 (in Russian).
- Vujkovic M., Keaton J.M., Lynch J.A., Miller D.R., Zhou J., Tcheandjieu C., Huffman J.E., Assimes T.L. [et al.]. Discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multi-ancestry meta-analysis. Nat. Genet., 2020, vol. 52, no. 7, pp. 680–691. DOI: 10.1038/s41588-020-0637-y
- Demidova T.Yu., Zenina S.G. Molecular genetic features of the diabetes mellitus development and the possibility of precision therapy. Diabetes mellitus, 2020, vol. 23, no. 5, pp. 467–474. DOI: 10.14341/DM12486 (in Russian).
- Avzaletdinova D.S., Morugova T.V., Sharipova L.F., Kochetova O.V. Association of polymorphic loci of susceptibi¬lity to diabetes mellitus type 2 in various ethnic groups of the Russian Federation. Diabetes mellitus, 2021, vol. 24, no. 3, pp. 262–272. DOI: 10.14341/DM12531 (in Russian).
- Li C., Yang Y., Liu X., Li Z., Liu H., Tan Q. Glucose metabolism-related gene polymorphisms as the risk predictors of type 2 diabetes. Diabetol. Metab. Syndr., 2020, vol. 12, no. 1, pp. 97. DOI: 10.1186/s13098-020-00604-5
- Saxena M., Dykes S.S., Malyarchuk S., Wang A.E., Cardelli J.A., Pruitt K. The sirtuins promote Dishevelled-1 scaf-folding of TIAM1, Rac activation and cell migration. Oncogene, 2015, vol. 34, no. 2, pp. 188–198. DOI: 10.1038/onc.2013.549
- Cao Y., Jiang X., Ma H., Wang Y., Xue P., Liu Y. SIRT1 and insulin resistance. J. Diabetes Complications, 2016, vol. 30, no. 1, pp. 178–183. DOI: 10.1016/j.jdiacomp.2015.08.022
- Han J., Wei M., Wang Q., Li X., Zhu C., Mao Y., Wei L., Sun Y., Jia W. Association of Genetic Variants of SIRT1 With Type 2 Diabetes Mellitus. Gene Expr., 2015, vol. 16, no. 4, pp. 177–185. DOI: 10.3727/105221615X14399878166195
- Rutter G.A., Pullen T.J., Hodson D.J., Martinez-Sanchez A. Pancreatic β-cell identity, glucose sensing and the control of insulin secretion. Biochem. J., 2015, vol. 466, no. 2, pp. 203–218. DOI: 10.1042/BJ20141384
- Muller Y.L., Piaggi P., Hoffman D., Huang K., Gene B., Kobes S., Thearle M.S., Knowler W.C. [et al.]. Common ge-netic variation in the glucokinase gene (GCK) is associated with type 2 diabetes and rates of carbohydrate oxidation and energy expenditure. Diabetologia, 2014, vol. 57, no. 7, pp. 1382–1390. DOI: 10.1007/s00125-014-3234-8
- Hu M., Cherkaoui I., Misra S., Rutter G.A. Functional Genomics in Pancreatic β Cells: Recent Advances in Gene De-letion and Genome Editing Technologies for Diabetes Research. Front. Endocrinol. (Lausanne), 2020, vol. 11, pp. 576632. DOI: 10.3389/fendo.2020.576632
- Beysel S., Eyerci N., Pinarli F.A., Kizilgul M., Ozcelik O., Caliskan M., Cakal E. HNF1A gene p.I27L is associated with early-onset, maturity-onset diabetes of the young-like diabetes in Turkey. BMC Endocr. Disord., 2019, vol. 19, no. 1, pp. 51. DOI: 10.1186/s12902-019-0375-2
- Mel’nikova E.S., Mustafina S.V., Rymar O.D., Ivanova A.A., Shcherbakova L.V., Bobak M., Maljutina S.K., Voe¬voda M.I., Maksimov V.N. Association of polymorphisms of genes SLC30A8 and MC4R with the prognosis of the development of type 2 diabetes mellitus. Diabetes mellitus, 2022, vol. 25, no. 3, pp. 215–225. DOI: 10.14341/DM12767 (in Russian).
- Fuchsberger C., Flannick J., Teslovich T.M., Mahajan A., Agarwala V., Gaulton K.J., Ma C., Fontanillas P. [et al.]. The genetic architecture of type 2 diabetes. Nature, 2016, vol. 536, no. 7614, pp. 41–47. DOI: 10.1038/nature18642
- Krentz N.A.J., Gloyn A.L. Insights into pancreatic islet cell dysfunction from type 2 diabetes mellitus genetics. Nat. Rev. Endocrinol., 2020, vol. 16, no. 4, pp. 202–212. DOI: 10.1038/s41574-020-0325-0
- Yoo H.J., Kim M., Kim M., Chae J.S., Lee S.-H., Lee J.H. The peptidylglycine-α-amidating monooxygenase (PAM) gene rs13175330 A>G polymorphism is associated with hypertension in a Korean population. Hum. Genomics, 2017, vol. 11, no. 1, pp. 29. DOI: 10.1186/s40246-017-0125-3
- Ghatan S., van Rooij J., van Hoek M., Boer C.G., Felix J.F., Kavousi M., Jaddoe V.W., Sijbrands E.J.G. [et al.]. De-fining type 2 diabetes polygenic risk scores through colocalization and network-based clustering of metabolic trait genetic asso-ciations. Genome Med., 2024, vol. 16, no. 1, pp. 10. DOI: 10.1186/s13073-023-01255-7
- Grarup N., Overvad M., Sparsø T., Witte D.R., Pisinger C., Jørgensen T., Yamauchi T., Hara K. [et al.]. The diabeto-genic VPS13C/C2CD4A/C2CD4B rs7172432 variant impairs glucose-stimulated insulin response in 5,722 non-diabetic Danish individuals. Diabetologia, 2011, vol. 54, no. 4, pp. 789–794. DOI: 10.1007/s00125-010-2031-2
- Isakova Zh.T., Talaibekova E.T., Asambaeva D.A., Kerimkulova A.S., Lunegova O.S., Aldasheva N.M., Aldashev A.A. Risk of type 2 diabetes mellitus in the Kyrgyz population in the presence of ADIPOQ (G276T), KCNJ11 (Glu23Lys), TCF7L2 (IVS3C>T) gene polymorphisms. Ter. Arkh., 2017, vol. 89, no. 10, pp. 40–47. DOI: 10.17116/terarkh2017891040-47 (in Russian).
- Haghvirdizadeh P., Mohamed Z., Abdullah N.A., Haghvirdizadeh P., Haerian M.S., Haerian B.S. KCNJ11: Genetic Polymorphisms and Risk of Diabetes Mellitus. J. Diabetes Res., 2015, vol. 2015, pp. 908152. DOI: 10.1155/2015/908152
- Binjawhar D.N., Ansari M.G.A., Sabico S., Hussain S.D., Alenad A.M., Alokail M.S., Al-Masri A.A., Al-Daghri N.M. Genetic Variants of HNF4A, WFS1, DUSP9, FTO, and ZFAND6 Genes Are Associated with Prediabetes Susceptibility and Inflammatory Markers in the Saudi Arabian Population. Genes (Basel), 2023, vol. 14, no. 3, pp. 536. DOI: 10.3390/genes14030536
- Hammad M.M., Abu-Farha M., Hebbar P., Anoop E., Chandy B., Melhem M., Channanath A., Al-Mulla F. [et al.]. The miR-668 binding site variant rs1046322 on WFS1 is associated with obesity in Southeast Asians. Front. Endocrinol. (Lausanne), 2023, vol. 14, pp. 1185956. DOI: 10.3389/fendo.2023.1185956
- Rao P., Wang H., Fang H., Gao Q., Zhang J., Song M., Zhou Y., Wang Y., Wang W. Association between IGF2BP2 Polymorphisms and Type 2 Diabetes Mellitus: A Case-Control Study and Meta-Analysis. Int. J. Environ. Res. Public Health, 2016, vol. 13, no. 6, pp. 574. DOI: 10.3390/ijerph13060574
- Shen L., Liu J., Zhao X., Wang A., Hu X. Association between insulin receptor substrate 1 gene polymorphism rs1801278 and gestational diabetes mellitus: an updated meta-analysis. Diabetol. Metab. Syndr., 2024, vol. 16, no. 1, pp. 62. DOI: 10.1186/s13098-024-01289-w
- Rasool S.U.A., Nabi M., Ashraf S., Amin S. Insulin Receptor Substrate 1 Gly972Arg (rs1801278) Polymorphism Is Associated with Obesity and Insulin Resistance in Kashmiri Women with Polycystic Ovary Syndrome. Genes (Basel), 2022, vol. 13, no. 8, рp. 1463. DOI: 10.3390/genes13081463
- Htwe T.N., Thein O.M., Hmone S.W., Thandar M. Prevalence of Insulin Receptor Substrate-1 Gene (G972R) Poly-morphism, Insulin Resistance, and Determination of β-Cell Function among Overweight and Obese Persons with Type 2 Diabetes Mellitus. J. ASEAN Fed. Endocr. Soc., 2021, vol. 36, no. 1, pp. 25–30. DOI: 10.15605/jafes.036.01.03
- Yousef A.A., Behiry E.G., Allah W.M.A., Hussien A.M., Abdelmoneam A.A., Imam M.H., Hikal D.M. IRS-1 genetic polymorphism (r.2963G>A) in type 2 diabetes mellitus patients associated with insulin resistance. Appl. Clin. Genet., 2018, vol. 11, pp. 99–106. DOI: 10.2147/TACG.S171096
- Sharma M., Aggarwal S., Nayar U., Vikram N.K., Misra A., Luthra K. Differential expression of insulin receptor sub-strate-1(IRS-1) in visceral and subcutaneous adipose depots of morbidly obese subjects undergoing bariatric surgery in a tertiary care center in north India; SNP analysis and correlation with metabolic profile. Diabetes Metab. Syndr., 2021, vol. 15, no. 3, pp. 981–986. DOI: 10.1016/j.dsx.2021.04.014
- Pei J., Wang B., Wang D. Current Studies on Molecular Mechanisms of Insulin Resistance. J. Diabetes Res., 2022, vol. 2022, pp. 1863429. DOI: 10.1155/2022/1863429
- Ijaz A., Babar S., Sarwar S., Shahid S.U., Shabana. The combined role of allelic variants of IRS-1 and IRS-2 genes in susceptibility to type2 diabetes in the Punjabi Pakistani subjects. Diabetol. Metab. Syndr., 2019, vol. 11, pp. 64. DOI: 10.1186/s13098-019-0459-1
- Liu K.-C., Leuckx G., Sakano D., Seymour P.A., Mattsson C.L., Rautio L., Staels W., Verdonck Y. [et al.]. Inhibition of Cdk5 promotes β-cell differentiation from ductal progenitors. Diabetes, 2018, vol. 67, no. 1, pp. 58–70. DOI: 10.2337/db16-1587
- Huang C., Guo Y., Li W., Xiang B., Zeng J., Zhou F., She L., Zhang P. [et al.]. Association of the CDKAL1 gene pol-ymorphism with gestational diabetes mellitus in Chinese women. BMJ Open Diabetes Res. Care, 2023, vol. 11, no. 2, pp. e003164. DOI: 10.1136/bmjdrc-2022-003164
- Asghar A., Firasat S., Afshan K., Naz S. Association of CDKAL1 gene polymorphism (rs10946398) with gestational diabetes mellitus in Pakistani population. Mol. Biol. Rep., 2023, vol. 50, no. 1, pp. 57–64. DOI: 10.1007/s11033-022-08011-x
- Xu N., Zhang T.-T., Han W.-J., Yin L.-P., Ma N.-Z., Shi X.-Y., Sun J.-J. Association of CDKAL1 RS10946398 Gene Polymorphism with Susceptibility to Diabetes Mellitus Type 2: A Meta-Analysis. J. Diabetes Res., 2021, vol. 2021, pp. 1254968. DOI: 10.1155/2021/1254968
- Galavi H., Mollashahee-Kohkan F., Saravani R., Sargazi S., Noorzehi N., Shahraki H. HHEX gene polymorphisms and type 2 diabetes mellitus: A case-control report from Iran. J. Cell. Biochem., 2019, vol. 120, no. 10, pp. 16445–16451. DOI: 10.1002/jcb.28788
- Heianza Y., Zhou T., Wang X., Furtado J.D., Appel L.J., Sacks F.M., Qi L. MTNR1B genotype and effects of carbo-hydrate quantity and dietary glycaemic index on glycaemic response to an oral glucose load: the OmniCarb trial. Diabetologia, 2024, vol. 67, no. 3, pp. 506–515. DOI: 10.1007/s00125-023-06056-6
- Stanzione R., Forte M., Cotugno M., Bianchi F., Marchitti S., Busceti C.L., Fornai F., Rubattu S. Uncoupling Protein 2 as a Pathogenic Determinant and Therapeutic Target in Cardiovascular and Metabolic Diseases. Curr. Neuropharmacol., 2022, vol. 20, no. 4, pp. 662–674. DOI: 10.2174/1570159X19666210421094204
- Xu L., Chen S., Zhan L. Association of uncoupling protein-2 -866G/A and Ala55Val polymorphisms with susceptibil-ity to type 2 diabetes mellitus: A meta-analysis of case-control studies. Medicine (Baltimore), 2021, vol. 100, no. 6, pp. e24464. DOI: 10.1097/MD.0000000000024464
- Azarova I., Klyosova E., Polonikov A. The Link between Type 2 Diabetes Mellitus and the Polymorphisms of Gluta-thione-Metabolizing Genes Suggests a New Hypothesis Explaining Disease Initiation and Progression. Life (Basel), 2021, vol. 11, no. 9, pp. 886. DOI: 10.3390/life11090886
- Howlader M., Sultana I., Akter F., Hossain M. Adiponectin gene polymorphisms associated with diabetes mellitus: A descriptive review. Heliyon, 2021, vol. 7, no. 8, pp. e07851
- Zhao N., Li N., Zhang S., Ma Q., Ma C., Yang X., Yin J., Zhang R. [et al.]. Associations between two common single nucleotide polymorphisms (rs2241766 and rs1501299) of ADIPOQ gene and coronary artery disease in type 2 diabetic patients: a systematic review and meta–analysis. Oncotarget, 2017, vol. 8, no. 31, pp. 51994–52005. DOI: 10.18632/oncotarget.18317
- Avzaletdinova D.S., Sharipova L.F., Kochetova O.V., Morugova T.V., Mustafina O.E. Association of adiponectin gene alleles with type 2 diabetes mellitus in residents of Bashkortostan. Problemy endokrinologii, 2019, vol. 65, no. 1, pp. 31–38. DOI: 10.14341/probl9426 (in Russian).
- Ghoshal K., Bhattacharyya M. Adiponectin: probe of the molecular paradigm associating diabetes and obesity. World J. Diabetes, 2015, vol. 6, no. 1, pp. 151–166. DOI: 10.4239/wjd.v6.i1.151
- Valeeva F.V., Kiseleva T.A., Khasanova K.B., Akhmetov I.I., Valeeva E.V., Nabiullina R.M. Analysis of associations of polymorphous markers of TCF7L2 gene with diabetes mellitus of the 2nd type in the case of residents of the Republic of Ta-tarstan. Meditsinskii al'manakh, 2017, no. 6 (51), pp. 126–129 (in Russian).
- De Luis D.A., Izaola O., Primo D., Gómez-Hoyos E., Ortola A., López-Gómez J.J., Aller R. Role of rs1501299 variant in the adiponectin gene on total adiponectin levels, insulin resistance and weight loss after a Mediterranean hypocaloric diet. Diabetes Res. Clin. Pract., 2019, vol. 148, pp. 262–267. DOI: 10.1016/j.diabres.2017.11.007
- Brovin D.L., Dracheva K.V., Panteleeva A.A., Belyaeva O.D., Pchelina S.N., Bazhenova E.A., Karonova T.L., Ko-lodina D.A. [et al.]. Gene ADIPOQ variants rs2441766 and rs266729: association with concentration of adiponectin (total and high molecular weight adiponectin), abdominal obesity and metabolic syndrome in women. Meditsinskaya genetika, 2019, vol. 18, no. 1, pp. 25–34. DOI: 10.25557/2073-7998.2019.01.25-34 (in Russian).
- Kaur H., Badaruddoza B., Bains V., Kaur A. Genetic association of ADIPOQ gene variants (–3971A>G and +276G>T) with obesity and metabolic syndrome in North Indian Punjabi population. PLoS One, 2018, vol. 13, no. 9, pp. e0204502. DOI: 10.1371/journal.pone.0204502
- Ouyang S., Cao D., Liu Z., Ma F., Wu J. Meta-analysis of the association of ADIPOQ G276T polymorphism with in-sulin resistance and blood glucose. Endocrine, 2014, vol. 47, no. 3, pp. 749–757. DOI: 10.1007/s12020-014-0317-8
- De Luis D.A., Pacheco D., Primo D., Izaola O., Aller R. The Association of SNP276G>T at Adiponectin Gene with Insulin Resistance and Circulating Adiponectin in Morbid Obese Patients after a Biliopancreatic Diversion Surgery. Obes. Surg., 2017, vol. 27, no. 12, pp. 3247–3252. DOI: 10.1007/s11695-017-2766-7
- Khodyrev D.S., Nikitin A.G., Brovkin A.N., Lavrikova E.Yu., Lebedeva N.O., Vikulova O.K., Shamkhalova M.Sh., Shestakova M.V. [et al.]. Association of polymorphisms of the ADIPOQ, ADIPOR1 and ADIPOR2 genes with type 2 diabetes mellitus. Diabetes mellitus, 2015, vol. 18, no. 2, pp. 5–11. DOI: 10.14341/DM201525-11 (in Russian).
- Shramko I., Ageeva E., Krutikov E., Maliy K., Repinskaya I., Fomochkina I., Kubishkin A., Gurtovaya A. [et al.]. Polymorphism in Adiponectin and Adiponectin Receptor Genes in Diabetes Mellitus Pathogenesis. Pathophysiology, 2022, vol. 29, no. 1, pp. 81–91. DOI: 10.3390/pathophysiology29010008
- Ievleva K.D., Bairova T.A., Rychkova L.V., Sheneman E.A., Khramova E.E., Kolesnikova L.I. Metabolism and obesity: role of leptin receptor gene. Acta Biomedica Scientifica, 2017, vol. 2, no. 5 (1), pp. 56–62. DOI: 10.12737/article_59e85cb55584e4.51145791 (in Russian).
- Isakova Zh.T., Talaibekova E.T., Zhyrgalbekova B.Zh., Mirrakhimov E.M., Aldasheva N.M., Aldashev A.A. Gene-gene interactions and the contribution of polymorphic loci of the KCNJ11, ADIPOQ, omentin, leptin, TCF7L2 and PPARg genes to the development of type 2 diabetes mellitus in the Kyrgyz population: a case-control genetic association study using MDR analysis. Problemy endokrinologii, 2018, vol. 64, no. 4, pp. 216–225. DOI: 10.14341/probl8344 (in Russian).
- Veerabathiran R., Aswathi P., Iyshwarya B., Rajasekaran D., Hussain Rs A. Genetic predisposition of LEPR (rs1137101) gene polymorphism related to type 2 diabetes mellitus – a meta-analysis. Ann. Med., 2023, vol. 55, no. 2, pp. 2302520. DOI: 10.1080/07853890.2024.2302520
- Mǎrginean C.O., Mǎrginean C., Meliţ L.E. New Insights Regarding Genetic Aspects of Childhood Obesity: A Mini-review. Front. Pediatr., 2018, vol. 6, pp. 271. DOI: 10.3389/fped.2018.00271
- Duan D.-M., Jhang J.-Y., Wu S., Teng M.-S., Hsu L.-A., Ko Y.-L. Modification effect of sex and obesity on the cor-relation of LEP polymorphisms with leptin levels in Taiwanese obese women. Mol. Genet. Genomic Med., 2020, vol. 8, no. 3, pp. e1113. DOI: 10.1002/mgg3.1113
- Al-Homedi Z., Afify N., Memon M., Alsafar H., Tay G., Jelinek H.F., Mousa M., Abu-Samra N., Osman W. Genetic Studies of Metabolic Syndrome in Arab Populations: A Systematic Review and Meta-Analysis. Front. Genet., 2021, vol. 12, pp. 733746. DOI: 10.3389/fgene.2021.733746
- Mikhailova S.V., Ivanoshchuk D.E. Innate-Immunity Genes in Obesity. J. Pers. Med., 2021, vol. 11, no. 11, pp. 1201. DOI: 10.3390/jpm11111201
- Zayani N., Omezzine A., Boumaiza I., Achour O., Rebhi L., Rejeb J., Rejeb N.B., Abdelaziz A.B., Bouslama A. As-sociation of ADIPOQ, leptin, LEPR, and resistin polymorphisms with obesity parameters in Hammam Sousse Sahloul Heart Study. J. Clin. Lab. Anal., 2017, vol. 31, no. 6, pp. e22148. DOI: 10.1002/jcla.22148
- Shramko Yu.I., Ageeva E.S., Malyi K.D., Repinskaya I.N., Tarimov C.O., Fomochkina I.I., Kubishkin A.V., Osta-penko O.V. [et al.]. Association between Adiponectin and Leptin Receptor Genetic Polymorphisms and Clinical Manifestations of Metabolic Syndrome. J. Diabetes Res., 2022, vol. 2022, pp. 9881422. DOI: 10.1155/2022/9881422
- Zhao Y.-K., Zhu X.-D., Liu R., Yang X., Liang Y.-L., Wang Y. The Role of PPARγ Gene Polymorphisms, Gut Microbiota in Type 2 Diabetes: Current Progress and Future Prospects. Diabetes Metab. Syndr. Obes., 2023, vol. 16, pp. 3557–3566. DOI: 10.2147/DMSO.S429825
- Dos Santos Rodrigues A.P., Pereira Souza Rosa L., Delleon da Silva H., de Paula Silveira-Lacerda E., Aparecida Sil-veira E. The Single Nucleotide Polymorphism PPARG2 Pro12Ala Affects Body Mass Index, Fat Mass, and Blood Pressure in Severely Obese Patients. J. Obes., 2018, vol. 2018, pp. 2743081. DOI: 10.1155/2018/2743081
- Pokushalov E., Ponomarenko A., Bayramova S., Garcia C., Pak I., Shrainer E., Voronina E., Sokolova E. [et al.]. Evaluating the Impact of Omega-3 Fatty Acid (SolowaysTM) Supplementation on Lipid Profiles in Adults with PPARG Poly-morphisms: A Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients, 2023, vol. 16, no. 1, pp. 97. DOI: 10.3390/nu16010097
- NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults. Lancet, 2024, vol. 403, no. 10431, pp. 1027–1050. DOI: 10.1016/S0140-6736(23)02750-2
- Yin D., Li Y., Liao X., Tian D., Xu Y., Zhou C., Liu J., Li S. [et al.]. FTO: a critical role in obesity and obesity-related diseases. Br. J. Nutr., 2023, vol. 130, no. 10, pp. 1657–1664. DOI: 10.1017/S0007114523000764
- Onalan E., Yakar B., Onalan E.E., Karakulak K., Kaymaz T., Donder E. m(6)A RNA, FTO, ALKBH5 expression in type 2 diabetic and obesity patients. J. Coll. Phys. Surg. Pak., 2022, vol. 32, no. 9, pp. 1143–1148. DOI: 10.29271/jcpsp.2022.09.1143
- Roumi Z., Salimi Z., Mahmoudi Z., Abbasi Mobarakeh K., Ladaninezhad M., Zeinalabedini M., Keshavarz Moham-madian M., Shamsi-Goushki A. [et al.]. Efficacy of a Comprehensive Weight Reduction Intervention in Male Adolescents With Different FTO Genotypes. Endocrinol. Diabetes Metab., 2024, vol. 7, no. 3, pp. e00483. DOI: 10.1002/edm2.483
- Cao Z., An Y., Lu Y. Altered N6-Methyladenosine Modification Patterns and Transcript Profiles Contributes to Cogni-tive Dysfunction in High-Fat Induced Diabetic Mice. Int. J. Mol. Sci., 2024, vol. 25, no. 4, pp. 1990. DOI: 10.3390/ijms25041990
- Duicu C., Mărginean C.O., Voidăzan S., Tripon F., Bănescu C. FTO rs 9939609 SNP Is Associated With Adiponectin and Leptin Levels and the Risk of Obesity in a Cohort of Romanian Children Population. Medicine (Baltimore), 2016, vol. 95, no. 20, pp. e3709. DOI: 10.1097/MD.0000000000003709
- Almeida S.M., Furtado J.M., Mascarenhas P., Ferraz M.E., Ferreira J.C., Monteiro M.P., Vilanova M., Ferraz F.P. Association between LEPR, FTO, MC4R, and PPARG-2 polymorphisms with obesity traits and metabolic phenotypes in school-aged children. Endocrine, 2018, vol. 60, no. 3, pp. 466–478. DOI: 10.1007/s12020-018-1587-3
- Chen J., Xiao W.-C., Zhao J.-J., Heitkamp M., Chen D.-F., Shan R., Yang Z.-R., Liu Z. FTO genotype and body mass index reduction in childhood obesity interventions: A systematic review and meta-analysis. Obes. Rev., 2024, vol. 25, no. 5, pp. e13715. DOI: 10.1111/obr.13715
- Lushchik M.L., Amel'yanovich M.D., Mosse I.B. Association of FTO gene polymorphisms with type 2 diabetes mellitus. Molekulyarnaya i prikladnaya genetika, 2022, vol. 32, pp. 73–80. DOI: 10.47612/1999-9127-2022-32-73-80 (in Rus-sian).
- Ji C., Chen X., Gao C., Jiao L., Wang J., Xu G., Fu H., Guo X., Zhao Y. IL-6 induces lipolysis and mitochondrial dysfunction, but does not affect insulin-mediated glucose transport in 3T3-L1 adipocytes. J. Bioenerg. Biomembr., 2011, vol. 43, no. 4, pp. 367–375. DOI: 10.1007/s10863-011-9361-8
- Markova T.N., Mishchenko N.K., Petina D.V. Adipocytokines: modern definition, classification and physiological role. Problemy endokrinologii, 2021, vol. 68, no. 1, pp. 73–80. DOI: 10.14341/probl12805 (in Russian).
- Leońska-Duniec A., Lepionka W., Brodkiewicz A., Buryta M. Association of the IL1A and IL6 polymorphisms with posttraining changes in body mass, composition, and biochemical parameters in Caucasian women. Biol. Sport., 2024, vol. 41, no. 2, pp. 47–56. DOI: 10.5114/biolsport.2024.131415
- Fang X., Miao R., Wei J., Wu H., Tian J. Advances in multi-omics study of biomarkers of glycolipid metabolism dis-order. Comput. Struct. Biotechnol. J., 2022, vol. 20, pp. 5935–5951. DOI: 10.1016/j.csbj.2022.10.030
- Manning A., Highland H.M., Gasser J., Sim X., Tukiainen T., Fontanillas P., Grarup N., Rivas M.A. [et al.]. A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk. Diabetes, 2017, vol. 66, no. 7, pp. 2019–2032. DOI: 10.2337/db16-1329
- Latva-Rasku A., Honka M.-J., Stančáková A., Koistinen H.A., Kuusisto J., Guan L., Manning A.K., Stringham H. [et al.]. A Partial Loss-of-Function Variant in AKT2 Is Associated With Reduced Insulin-Mediated Glucose Uptake in Multiple Insulin-Sensitive Tissues: A Genotype-Based Callback Positron Emission Tomography Study. Diabetes, 2018, vol. 67, no. 2, pp. 334–342. DOI: 10.2337/db17-1142
- Elangeeb M.E., Elfaki I., Elkhalifa M.A., Adam K.M., Alameen A.O., Kamaleldin Elfadl A., Altedlawi Albalawi I., Al-masoudi K.S. [et al.]. In Silico Investigation of AKT2 Gene and Protein Abnormalities Reveals Potential Association with Insulin Resistance and Type 2 Diabetes. Curr. Issues Mol. Biol., 2023, vol. 45, no. 9, pp. 7449–7475. DOI: 10.3390/cimb45090471
- Mohás M., Kisfali P., Járomi L., Maász A., Fehér E., Csöngei V., Polgár N., Sáfrány E. [et al.]. GCKR gene functional variants in type 2 diabetes and metabolic syndrome: do the rare variants associate with increased carotid intima-media thickness? Cardiovasc. Diabetol., 2010, vol. 9, pp. 79. DOI: 10.1186/1475-2840-9-79
- Ansari N., Ramachandran V., Mohamad N.A., Salim E., Ismail P., Hazmi M., Inchee Mat L.N. Association of GCK (rs1799884), GCKR (rs780094), and G6PC2 (rs560887) Gene Polymorphisms with Type 2 Diabetes among Malay Eth-nics. Glob. Med. Genet., 2023, vol. 10, no. 1, pp. 12–18. DOI: 10.1055/s-0042-1760384
- Rehman K., Akash M.S.H. Mechanisms of inflammatory responses and development of insulin resistance: how are they interlinked? J. Biomed. Sci., 2016, vol. 23, no. 1, pp. 87. DOI: 10.1186/s12929-016-0303-y
- Yin X., Xu Z., Zhang Z., Li L., Pan Q., Zheng F., Li H. Association of PI3K/AKT/mTOR pathway genetic variants with type 2 diabetes mellitus in Chinese. Diabetes Res. Clin. Pract., 2017, vol. 128, pp. 127–135. DOI: 10.1016/j.diabres.2017.04.002
- Hosseini Khorami S.A., Mutalib M.S.A., Feili Shiraz M., Abdullah J.A., Rejali Z., Ali R.M., Khaza'ai H. Genetic deter-minants of obesity heterogeneity in type II diabetes. Nutr. Metab. (Lond.), 2020, vol. 17, pp. 55. DOI: 10.1186/s12986-020-00476-6
- Dodington D.W., Desai H.R., Woo M. JAK/STAT ‒ Emerging Players in Metabolism. Trends Endocrinol. Metab., 2018, vol. 29, no. 1, pp. 55–65. DOI: 10.1016/j.tem.2017.11.001
- Gurzov E.N., Stanley W.J., Pappas E.G., Thomas H.E., Gough D.J. The JAK/STAT pathway in obesity and diabetes. FEBS J., 2016, vol. 283, no. 6, pp. 3002–3015. DOI: 10.1111/febs.13709
- Kanmani S., Kwon M., Shin M.-K., Kim M.K. Association of C-Reactive Protein with Risk of Developing Type 2 Diabetes Mellitus, and Role of Obesity and Hypertension: A Large Population–Based Korean Cohort Study. Sci. Rep., 2019, vol. 9, no. 1, pp. 4573. DOI: 10.1038/s41598-019-40987-8
- Dahlem C., Kado S.Y., He Y., Bein K., Wu D., Haarmann-Stemmann T., Kado N.Y., Vogel C.F.A. AHR Signaling Interacting with Nutritional Factors Regulating the Expression of Markers in Vascular Inflammation and Atherogenesis. Int. J. Mol. Sci., 2020, vol. 21, no. 21, pp. 8287. DOI: 10.3390/ijms21218287
- Topolyanskaya S.V. Tumor Necrosis Factor-Alpha and Age-Related Pathologies. Arkhiv" vnutrennei meditsiny, 2020, vol. 10, no. 6 (56), pp. 414–421. DOI: 10.20514/2226-6704-2020-10-6-414-421 (in Russian).
- Timper K., Denson J.L., Steculorum S.M., Heilinger C., Engström-Ruud L., Wunderlich C.M., Rose-John S., Wunderlich F.T., Brüning J.C. IL-6 Improves Energy and Glucose Homeostasis in Obesity via Enhanced Central IL-6 trans-Signaling. Cell Rep., 2017, vol. 19, no. 2, pp. 267–280. DOI: 10.1016/j.celrep.2017.03.043