Insulin receptor substrate-1 gene polymorphism and lipid panel data in type 2 diabetic patients with comorbid obesity and/or essential hypertension

Mariya Marushchak; Lyudmyla Mazur; Inna Krynytska

doi:10.2478/enr-2023-0001

Abstract

Objective. The hallmarks of type 2 diabetes mellitus (T2DM) are insulin resistance (IR) and insulin receptor substrate (IRS) proteins essential for the insulin signaling. IRS-1 gene has not only been shown to be associated with T2DM, but also has indicated that it may significantly correlate with diabetic complications, such as coronary heart disease and obesity. The aim of this study was to evaluate changes of the lipid panel data in T2DM patients with comorbid obesity and/or essential hypertension in connection with the IRS-1 (rs2943640) polymorphism.

Methods. The study involved 33 T2DM patients and 10 healthy individuals. The IRS-1 (rs2943640) polymorphism was genotyped using a TaqMan real-time polymerase chain reaction method. Blood serum lipid panel data were determined with commercially available kits using a Cobas 6000 analyzer.

Results. Analysis of the serum lipid panel data depending on the presence of the C/A alleles of IRS-1 (rs2943640) polymorphism in T2DM patients, regardless of the presence/absence of comorbidities, showed significantly lower level of high-density lipoprotein cholesterol (HDL-C) and significantly higher level of non-HDL-C in the carriers of C allele vs. carriers of A allele. In T2DM patients with comorbid obesity and essential hypertension, proatherogenic lipid changes were found in both C and A alleles carriers. Analysis of the effect of IRS-1 (rs2943640) genotypes on serum lipid panel data in T2DM patients, regardless of the presence/absence of comorbidities, showed that the CC genotype carriers had more pronounced pro-atherogenic changes vs. carriers of СА and АА genotypes. In the comorbid course of T2DM (both in combination with obesity and obesity and essential hypertension), pro-atherogenic changes were found in the carriers of the CA genotype of IRS-1 (rs2943640) polymorphism.

Conclusions. The presence of the C allele of IRS-1 (rs2943640) polymorphism in both homo-zygous and heterozygous states indicates increased risk of pro-atherogenic changes in T2DM patients with comorbid obesity and/or essential hypertension.

References

Akalu Y, Belsti Y. Hypertension and its associated factors among type 2 diabetes mellitus patients at Debre Tabor General Hospital, Northwest Ethiopia. Diabetes Metab Syndr Obes 13, 1621–1631, 2020.
Search in Google Scholar Back to article
Albegali AA, Shahzad M, Mahmood S, Ullah MI. Genetic association of insulin receptor substrate-1 (IRS-1, rs1801278) gene with insulin resistant of type 2 diabetes mellitus in a Pakistani population. Mol Biol Rep 46, 6065–6070, 2019.
Search in Google Scholar Back to article
American Diabetes Association. Standards of medical care in diabetes–2019 abridged for primary care providers. Clin Diabetes 37, 11–34, 2019.
Search in Google Scholar Back to article
Arikoglu H, Aksoy HM, Erkoc KD, Asik A, Ipekci SH, Iscioglu F. IRS1 gene polymorphisms Gly972Arg and Ala-513Pro are not associated with insulin resistance and type 2 diabetes risk in non-obese Turkish population. Meta Gene 2, 579–585, 2014.
Search in Google Scholar Back to article
Bhatt SP, Guleria R. Association of IRS1 (Gly972Arg) and IRS2 (Gly1057Asp) genes polymorphisms with OSA and NAFLD in Asian Indians. PLoS ONE 16, e0245408, 2021.
Search in Google Scholar Back to article
Bilous I, Pavlovych L, Krynytska I, Marushchak M, Kamyshnyi A. Apoptosis and cell cycle pathway-focused genes expression analysis in patients with different forms of thyroid pathology. Open Access Maced J Med Sci 8, 784–792, 2020.
Search in Google Scholar Back to article
Bilovol OM, Shalimova AS, Kochueva MM. Commorbidity of essential hypertension and type 2 diabetes mellitus is an actual problem of modern medicine. Ukrainian Therapeutical Journal 1, 11–17, 2014.
Search in Google Scholar Back to article
Blachnio-Zabielska AU, Roszczyc-Owsiejczuk K, Imierska M, Pogodzinska K, Rogalski P, Daniluk J, Zabielski P. CerS1 but not CerS5 gene silencing improves insulin sensitivity and glucose uptake in skeletal muscle. Cells 11, 206, 2022.
Search in Google Scholar Back to article
Bluher M, Stumvoll M. Diabetes and Obesity. In: Diabetes Complications, Comorbidities and Related Disorders (Bonora E, De Fronzo R. Ed.), Endocrinology, Springer, 1–49, 2018.
Search in Google Scholar Back to article
Colussi G, Da Porto A, Cavarape A. Hypertension and type 2 diabetes: lights and shadows about causality. J Hum Hypertens 34, 91–93, 2020.
Search in Google Scholar Back to article
Cosentino F, Grant PJ, Aboyans V, Bailey CJ, Ceriello A, Delgado V, Federici M, Filippatos G, Grobbee DE, Hansen TB, Huikuri HV, Johansson I, Juni P, Lettino M, Marx N, Mellbin LG, Ostgren CJ, Rocca B, Roffi M, Sattar N, Seferovic PM, Sousa-Uva M, Valensi P, Wheeler DC; ESC Scientific Document Group. 2019 ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J 41, 255–323, 2020.
Search in Google Scholar Back to article
Degen AS, Krynytska IY, Kamyshnyi AM. Changes in the transcriptional activity of the entero-insular axis genes in streptozotocin-induced diabetes and after the administration of TNF-alpha non-selective blockers. Endocr Regul 54,160–171, 2020.
Search in Google Scholar Back to article
Dworzynski P, Aasbrenn M, Rostgaard K, Melbye M, Gerds TA, Hjalgrim H, Pers TH. Nationwide prediction of type 2 diabetes comorbidities. Sci Rep 10, 1776, 2020.
Search in Google Scholar Back to article
Guerra-Lopez A. Hypertension and dyslipidemia. Cardiovasc Metab Sci 32, s273–s276, 2021.
Search in Google Scholar Back to article
Gupta S, Jhawat V. Induction of type 2 diabetes mellitus with antihypertensive therapy: is there any role of alpha adducin, ACE, and IRS-1 gene? Value Health Reg Issues 12C, 90–98, 2017.
Search in Google Scholar Back to article
He J, Qiu LX, Wang MY. Polymorphisms in the XPG gene and risk of gastric cancer in Chinese populations. Hum Genet 131, 1235–1244, 2012.
Search in Google Scholar Back to article
Hevko U, Kozak K, Krynytska I, Marushchak M. Diagnostic value of a complete blood count in type 2 diabetes mellitus and comorbidities. Arch Balk Med Union 55, 601–607, 2020.
Search in Google Scholar Back to article
Htwe TN, Thein OM, Hmone SW, Thandar M. Prevalence of insulin receptor substrate-1 gene (G972R) polymorphism, insulin resistance, and determination of β-cell function among overweight and obese persons with type 2 diabetes mellitus. J ASEAN Fed Endocr Soc 36, 25–30, 2021.
Search in Google Scholar Back to article
Ijaz A, Babar S, Sarwar S, Ullah S, 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 11, 64, 2019.
Search in Google Scholar Back to article
International Diabetes Federation. Diabetes facts & figures, 2019. (online) Available at: https://www.idf.org/aboutdiabetes/what-is-diabetes/facts-figures.html. [Accessed 2021 Aug 21]
Search in Google Scholar Back to article
Johnson LA, Maeda N. Macrovascular complications of diabetes in atherosclerosis prone mice. Expert Rev Endocrinol Metab 5, 89–98, 2010.
Search in Google Scholar Back to article
Kalninova J, Jakus V, Glejtkova M, Kuracka L, Sandorova E. Impact of glycemic control on advanced glycation and inflammation in overweight and obese patients with type 2 diabetes mellitus. Bratisl Lek Listy 115, 457–468, 2014.
Search in Google Scholar Back to article
Kochuieva M, Psarova V, Ruban L, Kyrychenko N, Alypova O, Matlai O, Shalimova A. Associations of IRS-1 polymorphism with various components of the metabolic syndrome in hypertensive patients. Wiad Lek 72, 1494–1498, 2019.
Search in Google Scholar Back to article
Kotsis V, Jordan J, Micic D, Finer N, Leitner DR, Toplak H, Tokgozoglu L, Athyros V, Elisaf M, Filippatos TD, Redon J, Redon P, Antza C, Tsioufis K, Grassi G, Seravalle G, Coca A, Sierra C, Lurbe E, Stabouli S, Jelakovic B, Nilsson PM. Obesity and cardiovascular risk: a call for action from the European Society of Hypertension Working Group of Obesity, Diabetes and the High-risk Patient and European Association for the Study of Obesity: part A: mechanisms of obesity induced hypertension, diabetes and dyslipidemia and practice guidelines for treatment. J Hypertens 36, 1427–1440, 2018.
Search in Google Scholar Back to article
Lastra G, Syed S, Kurukulasuriya LR, Manrique C, Sowers JR. Type 2 diabetes mellitus and hypertension: an update. Endocrinol Metab Clin North Am 43, 103–122, 2014.
Search in Google Scholar Back to article
Lavin DP, White MF, Brazil DP. IRS proteins and diabetic complications. Diabetologia 59, 2280–2291, 2016.
Search in Google Scholar Back to article
Long AN, Dagogo-Jack S. Comorbidities of diabetes and hypertension: mechanisms and approach to target organ protection. J Clin Hypertens 13, 244–251, 2011.
Search in Google Scholar Back to article
Mahajan A, Taliun D, Thurner M, Robertson NR, Torres JM, Rayner NW et al. Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps. Nat. Genet 50, 1505–1513, 2018.
Search in Google Scholar Back to article
Mahmutovic L, Bego T, Sterner M, Gremsperger G, Ahlqvist E, Velija Asimi Z, Prnjavorac B, Hamad N, Causevic A, Groop L, Semiz S. Association of IRS1 genetic variants with glucose control and insulin resistance in type 2 diabetic patients from Bosnia and Herzegovina. Drug Metab Pers Ther 34, 20180031, 2019.
Search in Google Scholar Back to article
Marushchak М, Krynytska I, Mazur L, Klishch I, Gabor G, Antonyshyn I. The relationship between experimental alimentary obesity and hard tooth tissues mineralization. Jord Med J 51, 25–33, 2017.
Search in Google Scholar Back to article
Marushchak M, Maksiv K, Krynytska I, Stechyshyn I. Glutathione antioxidant system of lymphocytes in the blood of patients in a setting of concomitant chronic obstructive pulmonary disease and arterial hypertension. Pol Merkur Lekarski 47, 177–182, 2019.
Search in Google Scholar Back to article
Marushchak M, Hevko U, Krynytska I. Insulin receptor substrate 1 gene variations and lipid profile characteristics in the type 2 diabetic patients with comorbid obesity and chronic pancreatitis. Endocr Regul 56, 101–109, 2022.
Search in Google Scholar Back to article
Musiienko VA, Marushchak MI. Genetic markers of type 2 diabetes. Medical and Clinical Chemistry 4, 184–191, 2020.
Search in Google Scholar Back to article
Piepoli MF, Hoes AW, Agewall S, et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice. Kardiologia Polska 74, 821–936, 2016.
Search in Google Scholar Back to article
Posokhova K, Stechyshyn I, Krynytska I, Marushchak M, Birchenko I, Klishch, I. Comparative study of the effect of various forms of quercetin on experimental diabetes. Rom J Diabetes Nutr Metab Dis 25, 383–388, 2018.
Search in Google Scholar Back to article
Prudente S, Di Paola R, Pezzilli S, Garofolo M, Lamacchia O, Filardi T, Mannino GC, Mercuri L, Alberico F, Scarale MG, Sesti G, Morano S, Penno G, Cignarelli M, Copetti M, Trischitta V. Pharmacogenetics of oral antidiabetes drugs: evidence for diverse signals at the IRS1 locus. Pharmacogenomics J 18, 431–435, 2018.
Search in Google Scholar Back to article
Repchuk Y, Sydorchuk LP, Sydorchuk AR, Fedonyuk LY, Kamyshnyi O, Korovenkova O, Plehutsa IM, Dzhuryak VS, Myshkovskii YM, Iftoda OM, Sydorchuk RI. Linkage of blood pressure, obesity and diabetes mellitus with angiotensinogen gene (AGT 704T>C/rs699) polymorphism in hypertensive patients. Bratisl Lek Listy 122, 715–720, 2021.
Search in Google Scholar Back to article
Scott RA, Scott LJ, Magi R, Marullo L, Gaulton KJ, Kaakinen M et al. Diabetes genetics replication and meta-analysis (DIAGRAM) consortium. An expanded genome-wide association study of type 2 diabetes in Europeans. Diabetes 66, 2888–2902, 2017.
Search in Google Scholar Back to article
Shalimova AS. Association of IRS>1 gene polymorphism with violations of blood lipid spectrum in patients with essential hypertension and concomitant type 2 diabetes. Family Medicine 3, 102–104, 2015.
Search in Google Scholar Back to article
Shalimova AS, Belovol AN. Metabolic homeostasis in different genotypes of IRS1 gene in comorbidity of hypertension, type 2 diabetes mellitus and obesity. Metabolic syndrome and modern methods of treatment of dys-metabolism: materials of the Republican scientific and practical conference, Tashkent 124–125, 2016.
Search in Google Scholar Back to article
Sikhayeva N, Iskakova A, Saigi-Morgui N, Zholdybaeva E, Eap CB, Ramanculov E. Association between 28 single nucleotide polymorphisms and type 2 diabetes mellitus in the Kazakh population: a case-control study. BMC Med Genet 18, 76, 2017.
Search in Google Scholar Back to article
Spannella F, Giulietti F, Di Pentima C, Sarzani R. Prevalence and control of dyslipidemia in patients referred for high blood pressure: The disregarded “double-trouble” lipid profile in overweight/obese. Adv Ther 36, 1426–1437, 2019.
Search in Google Scholar Back to article
Sydorchuk LP, Sokolenko AA, Sydorchuk AR, Kryklyvets LG, Biryuk IG, Fliundra IG, Sokolenko MA. Insulin resistance in patients with arterial hypertension and abdominal obesity depending on ACE and PPAR-γ2 genes polymorphism: A new opinion concerning an old problem. New Armen Med J 9, 43–51, 2015.
Search in Google Scholar Back to article
Sydorchuk LP, Serdulets YI, Fediv OI, Havrysh LO, Teleki YM, Sydorchuk AR, Kshanovska AI, Turubarova-Leunova NA, Lekhai DO. The polymorphism of matrilin-3 (rs77245812) and interleukin-10 (rs1800872) genes in osteoarthritis patients with arterial hypertension, obesity and type 2 diabetes mellitus. Arch Balk Med Union 52, 422–429, 2017.
Search in Google Scholar Back to article
Turner N, Cooney GJ, Kraegen EW, Bruce CR. Fatty acid metabolism, energy expenditure and insulin resistance in muscle. J Endocrinol 220, T61–T79, 2014.
Search in Google Scholar Back to article
Vassy JL, Hivert MF, Porneala B, Dauriz M, Florez JC, Dupuis J, Siscovick DS, Fornage M, Rasmussen-Torvik LJ, Bouchard C, Meigs JB. Polygenic type 2 diabetes prediction at the limit of common variant detection. Diabetes 63, 2172–2182, 2014.
Search in Google Scholar Back to article
Williams B, Mancia G, Spiering W, Rosei EA, Azizi M, Burnier M et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension. J Hypertens 36, 1953–2041, 2018.
Search in Google Scholar Back to article
Yiannakouris N, Cooper JA, Shah S, Drenos F, Ireland HA, Stephens JW, Li KW, Elkeles R, Godsland IF, Kivimaki M, Hingorani AD, Kumari M, Talmud PJ, Humphries SE. IRS1 gene variants, dysglycaemic metabolic changes and type-2 diabetes risk. Nutr Metab Cardiovasc Dis 22, 1024–1030, 2012.
Search in Google Scholar Back to article
Yousef AA, Behiry EG, Allah WMA, Hussien AM, Abdelmoneam AA, Imam MH, Hikal DM. IRS-1 genetic polymorphism (r.2963G>A) in type 2 diabetes mellitus patients associated with insulin resistance. Appl Clin Genet 11, 99–106, 2018.
Search in Google Scholar Back to article
Zhang D, Zhang X, Liu D, Liu T, Cai W, Yan C, Han Y. Association between insulin receptor substrate-1 polymorphisms and high platelet reactivity with clopidogrel therapy in coronary artery disease patients with type 2 diabetes mellitus. Cardiovasc Diabetol 15, 50, 2016.
Search in Google Scholar Back to article

Insulin receptor substrate-1 gene polymorphism and lipid panel data in type 2 diabetic patients with comorbid obesity and/or essential hypertension

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