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Current Vascular Pharmacology

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ISSN (Print): 1570-1611
ISSN (Online): 1875-6212

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General Research Article

Associations between Adiponectin Gene Variability, Proinflammatory and Angiogenetic Markers: Implications for Microvascular Disease Development in Type 2 Diabetes Mellitus?

Author(s): Christina Kollia, Alexios S. Antonopoulos, Gerasimos Siasos*, Theodosia Konsola, Evangelos Oikonomou, Nikolaos Gouliopoulos, Vasiliki Tsigkou, Aggeliki Papapanagiotou, Eva Kassi, Nicholas Tentolouris, Niki Katsiki, Manolis Vavuranakis, Athanasios G. Papavassiliou and Dimitris Tousoulis

Volume 17, Issue 2, 2019

Page: [204 - 208] Pages: 5

DOI: 10.2174/1570161116666180108113825

Price: $65

Abstract

Background: Adiponectin gene (ADIPOQ) variability may affect the risk for type 2 diabetes mellitus (T2DM) but it remains unclear whether it is involved in microvascular complications.

Objective: To explore the impact of ADIPOQ variability on markers of inflammation and angiogenesis in T2DM.

Methods: Overall, 220 consecutive T2DM patients from our outpatient diabetic clinic were genotyped for G276T (rs1501299) and T45G (rs2241766) single nucleotide polymorphisms of ADIPOQ gene. Serum levels of interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), vascular endothelial growth factor (VEGF) were measured by enzyme-linked immunosorbent assay and high sensitivity Creactive protein (hsCRP) by immunonephelometry.

Results: Homozygosity for the G allele on rs2241766 was associated with significantly lower serum VEGF and ICAM-1 levels compared with other genotype groups, but had no effect on IL-6. Genetic variability on rs1501299 was not associated with either VEGF or ICAM-1 levels, but T homozygotes for rs1501299 had significantly lower IL-6 concentrations compared with G carriers. Furthermore, the presence of the G allele on rs2241766 was associated with significantly lower HbA1c, whereas no associations were observed for both body mass index and hsCRP with either rs2241766 or rs1501299.

Conclusion: Genetic variability on adiponectin gene was associated with serum levels of inflammatory and angiogenetic markers. Further research is required to elucidate the role of adiponectin in the development and/or progression of microvascular disease in T2DM patients.

Keywords: ADIPOQ, adiponectin, angiogenesis, diabetes mellitus, inflammation, microvascular disease.

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[1]
Antoniades C, Antonopoulos AS, Tousoulis D, Stefanadis C. Adiponectin: From obesity to cardiovascular disease. Obes Rev 2009; 10: 269-79.
[2]
Antonopoulos AS, Margaritis M, Verheule S, et al. Mutual regulation of epicardial adipose tissue and myocardial redox state by PPAR-gamma/adiponectin signaling. Circ Res 2016; 118: 842-55.
[3]
Margaritis M, Antonopoulos AS, Digby J, et al. Interactions between vascular wall and perivascular adipose tissue reveal novel roles for adiponectin in the regulation of endothelial nitric oxide synthase function in human vessels. Circulation 2013; 127: 2209-21.
[4]
Antonopoulos AS, Tousoulis D, Antoniades C, et al. Genetic variability on adiponectin gene affects myocardial infarction risk: The role of endothelial dysfunction. Int J Cardiol 2013; 168: 326-30.
[5]
Antonopoulos AS, Margaritis M, Coutinho P, et al. Adiponectin as a link between type 2 diabetes and vascular NADPH oxidase activity in the human arterial wall: The regulatory role of perivascular adipose tissue. Diabetes 2015; 64: 2207-19.
[6]
Katsiki N, Mantzoros C, Mikhailidis DP. Adiponectin, lipids and atherosclerosis. Curr Opin Lipidol 2017; 28: 347-54.
[7]
Katsiki N, Yovos JG, Gotzamani-Psarrakou A, Karamitsos DT. Adipokines and vascular risk in type 2 diabetes mellitus. Angiology 2011; 62: 601-4.
[8]
Antonopoulos AS, Tousoulis D, Antoniades C, et al. Genetic variability on adiponectin gene affects myocardial infarction risk: The role of endothelial dysfunction. Int J Cardiol 2013; 168: 326-30.
[9]
Papaoikonomou S, Tousoulis D, Tentolouris N, et al. Assessment of the effects of the A3872G polymorphism on the C-reactive protein gene in patients with diabetes mellitus type 2. Int J Cardiol 2011; 151: 243-5.
[10]
Konsola T, Siasos G, Antonopoulos AS, et al. The impact of T786C and G894T polymorphisms of eNOS on vascular endothelial growth factor serum levels in type 2 diabetes patients. Int J Cardiol 2016; 222: 155-6.
[11]
Choe EY, Wang HJ, Kwon O, et al. Variants of the adiponectin gene and diabetic microvascular complications in patients with type 2 diabetes. Metabolism 2013; 62: 677-85.
[12]
Katsiki N, Mantzoros CS. Statins in relation to adiponectin: A significant association with clinical implications. Atherosclerosis 2016; 253: 270-2.
[13]
Kishida K, Funahashi T, Shimomura I. Adiponectin as a routine clinical biomarker. Best Pract Res Clin Endocrinol Metab 2014; 28: 119-30.
[14]
Rodriguez AJ, Nunes Vdos S, Mastronardi CA, Neeman T, Paz-Filho GJ. Association between circulating adipocytokine concentrations and microvascular complications in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of controlled cross-sectional studies. J Diabetes Complications 2016; 30: 357-67.
[15]
Katsiki N, Mikhailidis DP, Gotzamani-Psarrakou A, Yovos JG, Karamitsos D. Effect of various treatments on leptin, adiponectin, ghrelin and neuropeptide Y in patients with type 2 diabetes mellitus. Expert Opin Ther Targets 2011; 15: 401-20.
[16]
Chrusciel P, Sahebkar A, Rembek-Wieliczko M, et al. Impact of statin therapy on plasma adiponectin concentrations: A systematic review and meta-analysis of 43 randomized controlled trial arms. Atherosclerosis 2016; 253: 194-208.
[17]
Sahebkar A, Watts GF. Fibrate therapy and circulating adiponectin concentrations: A systematic review and meta-analysis of randomized placebo-controlled trials. Atherosclerosis 2013; 230: 110-20.
[18]
Dolezelova E, Stein E, Derosa G, Maffioli P, Nachtigal P, Sahebkar A. Effect of ezetimibe on plasma adipokines: A systematic review and meta-analysis. Br J Clin Pharmacol 2017; 83: 1380-96.
[19]
Rojas E, Rodriguez-Molina D, Bolli P, et al. The role of adiponectin in endothelial dysfunction and hypertension. Curr Hypertens Rep 2014; 16: 463.
[20]
Lim S, Quon MJ, Koh KK. Modulation of adiponectin as a potential therapeutic strategy. Atherosclerosis 2014; 233: 721-8.
[21]
Fisman EZ, Tenenbaum A. Adiponectin: A manifold therapeutic target for metabolic syndrome, diabetes, and coronary disease? Cardiovasc Diabetol 2014; 13: 103.
[22]
Li D, Xu X, Zhang Y, et al. Liraglutide treatment causes upregulation of adiponectin and downregulation of resistin in Chinese type 2 diabetes. Diabetes Res Clin Pract 2015; 110: 224-8.
[23]
Sahebkar A, Ponzo V, Bo S. Effect of Dipeptidyl Peptidase-4 Inhibitors on plasma adiponectin: A systematic review and meta-analysis of randomized controlled trials. Curr Med Chem 2016; 23: 1356-69.
[24]
Siasos G, Tousoulis D, Kollia C, et al. Adiponectin and cardiovascular disease: Mechanisms and new therapeutic approaches. Curr Med Chem 2012; 19: 1193-209.
[25]
Su JR, Lu ZH, Su Y, et al. Relationship of serum adiponectin levels and metformin therapy in patients with type 2 diabetes. Horm Metab Res 2016; 48: 92-8.
[26]
Bi Y, Zhang B, Xu W, et al. Effects of exenatide, insulin, and pioglitazone on liver fat content and body fat distributions in drug-naive subjects with type 2 diabetes. Acta Diabetol 2014; 51: 865-73.
[27]
Matsumura M, Nakatani Y, Tanka S, et al. Efficacy of additional canagliflozin administration to type 2 diabetes patients receiving insulin therapy: Examination of diurnal glycemic patterns using continuous glucose monitoring (CGM). Diabetes Ther 2017; 8: 821-7.
[28]
Okamoto A, Yokokawa H, Sanada H, Naito T. Changes in levels of biomarkers associated with adipocyte function and insulin and glucagon kinetics during treatment with dapagliflozin among obese type 2 diabetes mellitus patients. Drugs R D 2016; 16: 255-61.
[29]
Tobita H, Sato S, Miyake T, Ishihara S, Kinoshita Y. Effects of Dapagliflozin on Body Composition and Liver Tests in patients with nonalcoholic steatohepatitis associated with type 2 diabetes mellitus: a prospective, open-label, uncontrolled study. Curr Ther Res Clin Exp 2017; 87: 13-9.
[30]
Antonopoulos AS, Margaritis M, Coutinho P, et al. Reciprocal effects of systemic inflammation and brain natriuretic peptide on adiponectin biosynthesis in adipose tissue of patients with ischemic heart disease. Arterioscler Thromb Vasc Biol 2014; 34: 2151-9.
[31]
Chu H, Wang M, Zhong D, et al. AdipoQ polymorphisms are associated with type 2 diabetes mellitus: A meta-analysis study. Diabetes Metab Res Rev 2013; 29: 532-45.
[32]
Li ZP, Zhang M, Gao J, Zhou GY, Li SQ, An ZM. Relation between ADIPOQ gene polymorphisms and type 2 diabetes. Genes 2015; 6: 512-9.
[33]
Tu Y, Yu Q, Fan G, et al. Assessment of type 2 diabetes risk conferred by SNPs rs2241766 and rs1501299 in the ADIPOQ gene, a case/control study combined with meta-analyses. Mol Cell Endocrinol 2014; 396: 1-9.
[34]
Wang WL, Zhu H, Xie Y, Li J. Relation between ADIPOQ gene polymorphisms and type 2 diabetes in a Chinese population. Int J Clin Exp Med 2015; 8: 6124-8.
[35]
Yang H, Ye E, Si G, et al. Adiponectin gene polymorphism rs2241766 T/G is associated with response to pioglitazone treatment in type 2 diabetic patients from southern China. PLoS One 2014; 9: e112480.
[36]
Tabatabaei-Malazy O, Hasani-Ranjbar S, Amoli MM, et al. Gender-specific differences in the association of adiponectin gene polymorphisms with body mass index. Rev Diabet Stud 2010; 7: 241-6.
[37]
Kasim NB, Huri HZ, Vethakkan SR, Ibrahim L, Abdullah BM. Genetic polymorphisms associated with overweight and obesity in uncontrolled Type 2 diabetes mellitus. Biomarkers Med 2016; 10: 403-15.
[38]
Foucan L, Maimaitiming S, Larifla L, et al. Adiponectin gene variants, adiponectin isoforms and cardiometabolic risk in type 2 diabetic patients. J Diab Invest 2014; 5: 192-8.
[39]
Chiodini BD, Specchia C, Gori F, et al. Adiponectin gene polymorphisms and their effect on the risk of myocardial infarction and type 2 diabetes: An association study in an Italian population. Ther Adv Cardiovasc Dis 2010; 4: 223-30.
[40]
Sun K, Li Y, Wei C, Tong Y, Zheng H, Guo Y. Recessive protective effect of ADIPOQ rs1501299 on cardiovascular diseases with type 2 diabetes: A meta-analysis. Mol Cell Endocrinol 2012; 349: 162-9.
[41]
Ji ZY, Li HF, Lei Y, et al. Association of adiponectin gene polymorphisms with an elevated risk of diabetic peripheral neuropathy in type 2 diabetes patients. J Diabetes Complications 2015; 29: 887-92.

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