Abstract
Atherosclerosis and its cardiovascular complications are the main cause of death in diabetic patients. Patients with diabetes mellitus have a greater than 10-fold risk of cardiovascular disease in their lifetime. The carotid Intima-Media Thickness (cIMT), a surrogate marker for the presence and progression of atherosclerosis, predicts future cardiovascular events in asymptomatic subjects with Type 2 Diabetes Mellitus (T2DM). This review focuses on genetic variants that contribute to the pathobiology of subclinical atherosclerosis in the setting of T2DM. Specifically, we devoted our attention to wellstudied genes selected for their relevance for atherosclerosis. These include: The Renin-Angiotensin- Aldosterone System (RAAS), Apolipoprotein E (ApoE), Methylenetetrahydrofolate Reductase (MTHFR) and pro-inflammatory genes.
The ever-growing availability of advanced genotyping technologies has made Genome-Wide Association Studies (GWAS) possible. Although several bioinformatics tools have been developed to manage and interpret the huge amounts of data produced, there has been limited success in the many attempts to uncover the biological meaning of the novel susceptibility loci for atherosclerosis.
Keywords: Type 2 diabetes mellitus, subclinical atherosclerosis, carotid intima-media thickness, genetic risk factors, RAAS, GWAS.
Graphical Abstract
[1]
Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract 2014; 103(2): 137-49.
[2]
Zimmet PZ, Magliano DJ, Herman WH, Shaw JE. Diabetes: A 21st century challenge. Lancet Diabetes Endocrinol 2014; 2(1): 56-64.
[3]
Paneni F, Beckman JA, Creager MA, Cosentino F. Diabetes and vascular disease: Pathophysiology, clinical consequences, and medical therapy: Part I. Eur Heart J 2013; 34(31): 2436-43.
[4]
Marso SP, Hiatt WR. Peripheral arterial disease in patients with diabetes. J Am Coll Cardiol 2006; 47(5): 921-9.
[5]
Forbang NI, McDermott MM, Liao Y, et al. Associations of diabetes mellitus and other cardiovascular disease risk factors with decline in the ankle-brachial index. Vasc Med 2014; 19(6): 465-72.
[6]
Lüscher TF, Creager MA, Beckman JA, Cosentino F. Diabetes and vascular disease: Pathophysiology, clinical consequences and medical therapy: Part II. Circulation 2003; 108(13): 1655-61.
[7]
Uusitupa M, Siitonen O, Aro A, Pyörälä K. Prevalence of coronary heart disease, left ventricular failure and hypertension in middle-aged, newly diagnosed type 2 (non-insulin-dependent) diabetic subjects. Diabetologia 1985; 28(1): 22-7.
[8]
Toth PP. Subclinical atherosclerosis: What it is, what it means and what we can do about it. Int J Clin Pract 2008; 62(8): 1246-54.
[9]
Shani J, Chen O. Imaging modalities to identity inflammation in an atherosclerotic plaque. Radiol Res Pract 2015; 410967.
[10]
Pignoli P, Tremoli E, Poli A, Oreste P, Paoletti R. Intimal plus medial thickness of the arterial wall: a direct measurement with ultrasound imaging. Circulation 1986; 74(6): 1399-406.
[11]
Sunil KK, Lakshmi AY, Srinivasa Rao PV, Das GC, Siva KV. Carotid intima-media thickness in patients with end-stage renal disease. Indian J Nephrol 2009; 19(1): 13-4.
[12]
Shah PK. Screening asymptomatic subjects for subclinical atherosclerosis: Can we, does it matter, and should we? J Am Coll Cardiol 2010; 56(2): 98-105.
[13]
Burke AP, Kolodgie FD, Zieske A, et al. Morphologic findings of coronary atherosclerotic plaques in diabetics: A postmortem study. Arterioscler Thromb Vasc Biol 2004; 24(7): 1266-71.
[14]
Moreno PR, Murcia AM, Palacios IF, et al. Coronary composition and macrophage infiltration in atherectomy specimens from patients with diabetes mellitus. Circulation 2000; 102(18): 2180-4.
[15]
Edsfeldt A, Gonçalves I, Grufman H, et al. Impaired fibrous repair: a possible contributor to atherosclerotic plaque vulnerability in patients with type II diabetes. Arterioscler Thromb Vasc Biol 2014; 34(9): 2143-50.
[16]
Siracuse JJ, Chaikof EL. The pathogenesis of diabetic atherosclerosis.In: Shrikhande GV, McKinsey JF, EdsDiabetes and peripheral vascular disease: Diagnosis and Management1st ed Springer New York. 2012; pp. 13-26.
[17]
Rahimi R, Nikfar S, Larijani B, Abdollahi M. A review on the role of antioxidants in the management of diabetes and its complications. Biomed Pharmacother 2005; 59(7): 365-73.
[18]
Tibaut M, Petrovič D. Oxidative stress genes, antioxidants and coronary artery disease in type 2 diabetes mellitus. Cardiovasc Hematol Agents Med Chem 2016; 14(1): 23-38.
[19]
Nathan DM, Cleary PA, Backlund JY, et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 2005; 353(25): 2643-53.
[20]
Mohlke KL, Boehnke M, Abecasis GR. Metabolic and cardiovascular traits: An abundance of recently identified common genetic variants. Hum Mol Genet 2008; 17(2): 102-8.
[21]
Martín-Timón I, Sevillano-Collantes C, Segura-Galindo A, Del Cañizo-Gómez FJ. Type 2 diabetes and cardiovascular disease: Have all risk factors the same strength? World J Diabetes 2014; 5(4): 444-70.
[22]
Wang L, Beecham A, Zhuo D, et al. Fine mapping study reveals novel candidate genes for carotid intima-media thickness in dominican republican families. Circ Cardiovasc Genet 2012; 5: 234-41.
[23]
Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 1990; 86(4): 1343-6.
[24]
Bonithon-Kopp C, Ducimetière P, Touboul PJ, et al. Plasma angiotensin-converting enzyme activity and carotid wall thickening. Circulation 1994; 89(3): 952-4.
[25]
He Q, Fan C, Yu M, et al. Associations of ACE gene insertion/deletion polymorphism, ACE activity, and ACE mRNA expression with hypertension in a Chinese population. PLoS One 2013; 8(10): e75870.
[26]
Castellano M, Muiesan ML, Rizzoni D, et al. Angiotensin-converting enzyme I/D polymorphism and arterial wall thickness in a general population. Circulation 1995; 91(11): 2721-4.
[27]
Pujia A, Motti C, Irace C, et al. Deletion polymorphism in angiotensin converting enzyme gene associated with carotid wall thickening in a healthy male population. Coron Artery Dis 1996; 7(1): 51-5.
[28]
Islam MS, Lehtimäki T, Juonala M, et al. Polymorphism of the angiotensin-converting enzyme (ACE) and angiotesinogen (AGT) genes and their associations with blood pressure and carotid artery intima media thickness among healthy Finnish young adults-the cardiovascular risk in young Finns study. Atherosclerosis 2006; 188(2): 316-22.
[29]
Sticchi E, Romagnuolo I, Sofi F, et al. Association between polymorphisms of the renin angiotensin system and carotid stenosis. J Vasc Surg 2011; 54(2): 467-73.
[30]
Kogawa K, Nishizawa Y, Hosoi M, et al. Effect of polymorphism of apolipoprotein E and angiotensin-converting enzyme genes on arterial wall thickness. Diabetes 1997; 46(4): 682-7.
[31]
Merlo S, Novák J, Tkáčová N, et al. Association of the ACE rs4646994 and rs4341 polymorphisms with the progression of carotid atherosclerosis in Slovenian patients with type 2 diabetes mellitus. Balkan J Med Genet 2016; 18(2): 37-42.
[32]
Saitou M, Osonoi T, Kawamori R, et al. Genetic risk factors and the anti-atherosclerotic effect of pioglitazone on carotid atherosclerosis of subjects with type 2 diabetes--a retrospective study. J Atheroscler Thromb 2010; 17(4): 386-94.
[33]
Bowden DW, Lehtinen AB, Ziegler JT, et al. Genetic epidemiology of subclinical cardiovascular disease in the diabetes heart study. Ann Hum Genet 2008; 72(5): 598-610.
[34]
Paternoster L, Martinez-Gonzalez NA, Charleton R, Chung M, Lewis S, Sudlow CL. Genetic effects on carotid intima-media thickness: systematic assessment and meta-analyses of candidate gene polymorphisms studied in more than 5000 subjects. Circ Cardiovasc Genet 2010; 3(1): 15-21.
[35]
Diamantopoulos EJ, Andreadis E, Kakou M, et al. Atherosclerosis of carotid arteries and the ace insertion/deletion polymorphism in subjects with diabetes mellitus type 2. Int Angiol 2002; 21(1): 63-9.
[36]
Burdon KP, Langefeld CD, Wagenknecht LE, et al. Association analysis of genes in the renin-angiotensin system with subclinical cardiovascular disease in families with Type 2 diabetes mellitus: The Diabetes Heart Study. Diabet Med 2006; 23(3): 228-34.
[37]
Yamasaki Y, Katakami N, Sakamoto K, et al. Combination of multiple genetic risk factors is synergistically associated with carotid atherosclerosis in Japanese subjects with type 2 diabetes. Diabetes Care 2006; 29(11): 2445-51.
[38]
Piao L, Tanaka Y, Nomiyama T, et al. Combined genotypes of ACE and NADPH oxidase p22phox associated with somatic mutation of mtDNA and carotid intima-media thickness in Japanese patients with type 2 diabetes mellitus. Curr Ther Res Clin Exp 2002; 63: 842-52.
[39]
Ambler SK, Brown RD. Genetic determinants of blood pressure regulation. J Cardiovasc Nurs 1999; 13(4): 59-77.
[40]
Mehri S, Koubaa N, Hammami S, et al. Genotypic interactions of renin-angiotensin system genes with diabetes type 2 in a Tunisian population. Life Sci 2010; 87(1-2): 49-54.
[41]
Chang HR, Cheng CH, Shu KH, Chen CH, Lian JD, Wu MY. Study of the polymorphism of angiotensinogen, angiotensin-converting enzyme and angiotensin receptor in type II diabetes with end-stage renal disease in Taiwan. J Chin Med Assoc 2003; 66(1): 51-6.
[42]
Merlo S, Jovana NS, Sara M, et al. Polymorphisms rs699 and rs4762 of the angiotensinogen gene and progression of carotid atherosclerosis in patients with type 2 diabetes mellitus. J Diabetic Complications Med 2016; 1: 1-5.
[43]
Al-Najai M, Muiya P, Tahir AI, et al. Association of the angiotensinogen gene polymorphism with atherosclerosis and its risk traits in the Saudi population. BMC Cardiovasc Disord 2013; 13: 17.
[44]
Xu MQ, Ye Z, Hu FB, He L. Quantitative assessment of the effect of angiotensinogen gene polymorphisms on the risk of coronary heart disease. Circulation 2007; 116(12): 1356-66.
[45]
Liang X, Qiu J, Liu X, et al. Polymorphism of angiotensinogen gene M235T in myocardial infarction and brain infarction: A meta-analysis. Gene 2013; 529(1): 73-9.
[46]
Liang B, Qin L, Wei H, et al. AGT M235T polymorphisms and ischemic stroke risk: A meta-analysis. J Neurol Sci 2013; 1(1-2): 118-25.
[47]
Wang WZ. Association between T174M polymorphism in the angiotensinogen gene and risk of coronary artery disease: A meta-analysis. J Geriatr Cardiol 2013; 10(1): 59-65.
[48]
Kretowski A, McFann K, Hokanson JE, et al. Polymorphisms of the renin-angiotensin system genes predict progression of subclinical coronary atherosclerosis. Diabetes 2007; 56(3): 863-71.
[49]
Lin J, Hu FB, Qi L, Curhan GC. Genetic polymorphisms of angiotensin-2 type 1 receptor and angiotensinogen and risk of renal dysfunction and coronary heart disease in type 2 diabetes mellitus. BMC Nephrol 2009; 10: 9.
[50]
Yazdanpanah M, Aulchenko YS, Hofman A, et al. Effects of the renin-angiotensin system genes and salt sensitivity genes on blood pressure and atherosclerosis in the total population and patients with type 2 diabetes. Diabetes 2007; 56(7): 1905-12.
[51]
Rahimi Z, Moradi M, Nasri H. A systematic review of the role of renin angiotensin aldosterone system genes in diabetes mellitus, diabetic retinopathy and diabetic neuropathy. J Res Med Sci 2014; 19(11): 1090-8.
[52]
Perry RJ, Samuel VT, Petersen KF, Shulman GI. The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes. Nature 2014; 510(7503): 84-91.
[53]
Sun Z, Lazar MA. Dissociating fatty liver and diabetes. Trends Endocrinol Metab 2013; 24(1): 4-12.
[54]
Ferreira CN, Carvalho MG, Fernandes AP, et al. Comparative study of apolipoprotein-E polymorphism and plasma lipid levels in dyslipidemic and asymptomatic subjects, and their implication in cardio/cerebro-vascular disorders. Neurochem Int 2010; 56(1): 177-82.
[55]
Grundy SM. Drug therapy of the metabolic syndrome: Minimizing the emerging crisis in polypharmacy. Nat Rev Drug Discov 2006; 5(4): 295-309.
[56]
Singh PP, Singh M, Mastana SS. APOE distribution in world populations with new data from India and the UK. Ann Hum Biol 2006; 33(3): 279-308.
[57]
Horejsí B, Ceska R. Apolipoproteins and atherosclerosis. Apolipoprotein E and apolipoprotein(a) as candidate genes of premature development of atherosclerosis. Physiol Res 2000; 49(Suppl. 1): 63-9.
[58]
Eichner JE, Dunn ST, Perveen G, Thompson DM, Stewart KE, Stroehla BC. Apolipoprotein E polymorphism and cardiovascular disease: A huge review. Am J Epidemiol 2002; 155(6): 487-95.
[59]
Guang-da X, You-ying L, Zhi-song C, Yu-sheng H, Xiang-jiu Y. Apolipoprotein E4 allele is predictor of coronary artery disease death in elderly patients with type 2 diabetes mellitus. Atherosclerosis 2004; 175(1): 77-81.
[60]
Chaudhary R, Likidlilid A, Peerapatdit T, et al. Apolipoprotein E gene polymorphism: Effects on plasma lipids and risk of type 2 diabetes and coronary artery disease. Cardiovasc Diabetol 2012; 11: 36.
[61]
Coto E, Gómez J, Tavira B, et al. A common APOE polymorphism is an independent risk factor for reduced glomerular filtration rate in the Spanish RENASTUR cohort. Cardiorenal Med 2013; 3(2): 113-9.
[62]
Manolio TA, Boerwinkle E, O’Donnell CJ, Wilson AF. Genetics of ultrasonographic carotid atherosclerosis. Arterioscler Thromb Vasc Biol 2004; 24(9): 1567-77.
[63]
Vauhkonen I, Niskanen L, Ryynänen M, et al. Divergent association of apolipoprotein E polymorphism with vascular disease in patients with NIDDM and control subjects. Diabet Med 1997; 14(9): 748-56.
[64]
Xiang GD, Hu TH, Wang YL. Apolipoprotein E genotypes and carotid artery atherosclerosis in type 2 diabetes mellitus. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2003; 20(1): 66-8.
[65]
Goyette P, Sumner JS, Milos R, et al. Human methylenetetrahydrofolate reductase: Isolation of cDNA mapping and mutation identification. Nat Genet 1994; 7(4): 551.
[66]
Kang SS, Wong PW, Malinow MR. Hyperhomocyst(e)inemia as a risk factor for occlusive vascular disease. Annu Rev Nutr 1992; 12: 279-98.
[67]
Robinson K, Mayer EL, Miller DP, et al. Hyperhomocysteinemia and low pyridoxal phosphate. Common and independent reversible risk factors for coronary artery disease. Circulation 1995; 92(10): 2825-30.
[68]
Verhoef P, Hennekens CH, Malinow MR, Kok FJ, Willett WC, Stampfer MJ. A prospective study of plasma homocyst(e)ine and risk of ischemic stroke. Stroke 1994; 25(10): 1924-30.
[69]
Boushey CJ, Beresford SA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA 1995; 274(13): 1049-57.
[70]
Chico A, Pérez A, Córdoba A, et al. Plasma homocysteine is related to albumin excretion rate in patients with diabetes mellitus: A new link between diabetic nephropathy and cardiovascular disease? Diabetologia 1998; 41(6): 684-93.
[71]
Emoto M, Kanda H, Shoji T, et al. Impact of insulin resistance and nephropathy on homocysteine in type 2 diabetes. Diabetes Care 2001; 24(3): 533-8.
[72]
Agulló-Ortuño MT, Albaladejo MD, Parra S, et al. Plasmatic homocysteine concentration and its relationship with complications associated to diabetes mellitus. Clin Chim Acta 2002; 326(1-2): 105-12.
[73]
Rudy A, Kowalska I, Straczkowski M, Kinalska I. Homocysteine concentrations and vascular complications in patients with type 2 diabetes. Diabetes Metab 2005; 31(2): 112-7.
[74]
Platt DE, Hariri E, Salameh P, et al. Type II diabetes mellitus and hyperhomocysteinemia: A complex interaction. Diabetol Metab Syndr 2017; 9: 19.
[75]
Mazza A, Bossone E, Mazza F, Distante A. Reduced serum homocysteine levels in type 2 diabetes. Nutr Metab Cardiovasc Dis 2005; 15(2): 118-24.
[76]
Diakoumopoulou E, Tentolouris N, Kirlaki E, et al. Plasma homocysteine levels in patients with type 2 diabetes in a Mediterranean population: Relation with nutritional and other factors. Nutr Metab Cardiovasc Dis 2005; 15(2): 109-17.
[77]
Evans RW, Shaten BJ, Hempel JD, et al. Homocyst(e)ine and risk of cardiovascular disease in the multiple risk factor intervention trial. Indian Heart J 2000; 52(7)(Suppl.): 44-52.
[78]
Frosst P, Blom HJ, Milos R, et al. A candidate genetic risk factor for vascular disease: A common mutation in methylenetetrahydrofolate reductase. Nat Genet 1995; 10(1): 111-3.
[79]
Weisberg I, Tran P, Christensen B, Sibani S, Rozen R. A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab 1998; 64(3): 169-72.
[80]
Weisberg IS, Jacques PF, Selhub J, et al. The 1298A->C polymorphism in methylenetetrahydrofolate reductase (MTHFR): In vitro expression and association with homocysteine. Atherosclerosis 2001; 156(2): 409-15.
[81]
Brattström L, Wilcken DE, Ohrvik J, Brudin L. Common methylenetetrahydrofolate reductase gene mutation leads to hyperhomocysteinemia but not to vascular disease: The result of a meta-analysis. Circulation 1998; 98(23): 2520-6.
[82]
Zhong JH, Rodríguez AC, Yang NN, Li LQ. Methylenetetrahydrofolate reductase gene polymorphism and risk of type 2 diabetes mellitus. PLoS One 2013; 8(9): e74521.
[83]
Niu W, Qi Y. An updated meta-analysis of methylenetetrahydrofolate reductase gene 677C/T polymorphism with diabetic nephropathy and diabetic retinopathy. Diabetes Res Clin Pract 2012; 95(1): 110-8.
[84]
Sun J, Xu Y, Zhu Y, Lu H. Methylenetetrahydrofolate reductase gene polymorphism, homocysteine and risk of macroangiopathy in Type 2 diabetes mellitus. J Endocrinol Invest 2006; 29(9): 814-20.
[85]
Hasegawa G, Obayashi H, Kamiuchi K, et al. The association between end-stage diabetic nephropathy and methylenetetrahydrofolate reductase genotype with macroangiopathy in type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes 2003; 111(3): 132-8.
[86]
Mazza A, Motti C, Nulli A, et al. Lack of association between carotid intima-media thickness and methylenetetrahydrofolate reductase gene polymorphism or serum homocysteine in non-insulin-dependent diabetes mellitus. Metabolism 2000; 49(6): 718-23.
[87]
Szabó GV, Kunstár A, Acsády G. Methylentetrahydrofolate reductase and nitric oxide synthase polymorphism in patients with atherosclerosis and diabetes. Pathol Oncol Res 2009; 15(4): 631-7.
[88]
Kaye JM, Stanton KG, McCann VJ, et al. Homocysteine, folate, methylene tetrahydrofolate reductase genotype and vascular morbidity in diabetic subjects. Clin Sci (Lond) 2002; 102(6): 631-7.
[89]
Pollex RL, Mamakeesick M, Zinman B, Harris SB, Hanley AJ, Hegele RA. Methylenetetrahydrofolate reductase polymorphism 677C>T is associated with peripheral arterial disease in type 2 diabetes. Cardiovasc Diabetol 2005; 4: 17.
[90]
Russo GT, Di Benedetto A, Magazzù D, et al. Mild hyperhomocysteinemia, C677T polymorphism on methylenetetrahydrofolate reductase gene and the risk of macroangiopathy in type 2 diabetes: A prospective study. Acta Diabetol 2011; 48(2): 95-101.
[91]
Buysschaert M, Dramais AS, Wallemacq PE, Hermans MP. Hyperhomocysteinemia in type 2 diabetes: Relationship to macroangiopathy, nephropathy, and insulin resistance. Diabetes Care 2000; 23(12): 1816-22.
[92]
Scaglione L, Gambino R, Rolfo E, et al. Plasma homocysteine, methylenetetrahydrofolate reductase gene polymorphism and carotid intima-media thickness in Italian type 2 diabetic patients. Eur J Clin Invest 2002; 32(1): 24-8.
[93]
Arai K, Yamasaki Y, Kajimoto Y, et al. Association of methylenetetrahydrofolate reductase gene polymorphism with carotid arterial wall thickening and myocardial infarction risk in NIDDM. Diabetes 1997; 46(12): 2102-4.
[94]
Ramji DP, Davies TS. Cytokines in atherosclerosis: Key players in all stages of disease and promising therapeutic targets. Cytokine Growth Factor Rev 2015; 26(6): 673-85.
[95]
Moreno PR, Fuster V. New aspects in the pathogenesis of diabetic atherothrombosis. J Am Coll Cardiol 2004; 44(12): 2293-300.
[96]
Pickup JC, Mattock MB, Chusney GD, Burt D. NIDDM as a disease of the innate immune system: Association of acute-phase reactants and interleukin-6 with metabolic syndrome X. Diabetologia 1997; 40(11): 1286-92.
[97]
Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 2001; 286(3): 327-34.
[98]
Festa A, D’Agostino R Jr, Tracy RP, Haffner SM. Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes: The insulin resistance atherosclerosis study. Diabetes 2002; 51(4): 1131-7.
[99]
Hu FB, Meigs JB, Li TY, Rifai N, Manson JE. Inflammatory markers and risk of developing type 2 diabetes in women. Diabetes 2004; 53(3): 693-700.
[100]
Lechleitner M, Herold M, Dzien-Bischinger C, Hoppichler F, Dzien A. Tumour necrosis factor-alpha plasma levels in elderly patients with Type 2 diabetes mellitus-observations over 2 years. Diabet Med 2002; 19(11): 949-53.
[101]
Kado S, Nagata N. Circulating intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin in patients with type 2 diabetes mellitus. Diabetes Res Clin Pract 1999; 46(2): 143-8.
[102]
Meigs JB, Hu FB, Rifai N, Manson JE. Biomarkers of endothelial dysfunction and risk of type 2 diabetes mellitus. JAMA 2004; 291(16): 1978-86.
[103]
Herder C, Baumert J, Thorand B, et al. Chemokines as risk factors for type 2 diabetes: results from the MONICA/KORA Augsburg study 1984-2002. Diabetologia 2006; 49(5): 921-9.
[105]
Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin
Endocrinol Metab 200; 89(6): 2548-56
[108]
Qu B, Qu T. Causes of changes in carotid intima-media thickness: A literature review. Cardiovasc Ultrasound 2015; 13: 46.
[109]
Banerjee M, Saxena M. Genetic polymorphisms of cytokine genes in type 2 diabetes mellitus. World J Diabetes 2014; 5(4): 493-504.
[110]
Fernández-Real JM, Ricart W. Insulin resistance and chronic cardiovascular inflammatory syndrome. Endocr Rev 2003; 24(3): 278-301.
[111]
Vozarova B, Fernández-Real JM, Knowler WC, et al. The interleukin-6 (-174) G/C promoter polymorphism is associated with type-2 diabetes mellitus in native Americans and Caucasians. Hum Genet 2003; 112(4): 409-13.
[112]
Illig T, Bongardt F, Schöpfer A, et al. Significant association of the interleukin-6 gene polymorphisms C-174G and A-598G with type 2 diabetes. J Clin Endocrinol Metab 2004; 89(10): 5053-8.
[113]
Papaoikonomou S, Tousoulis D, Tentolouris N, et al. Assessment of the effects of 174G/C polymorphism on interleukin 6 gene on macrovascular complications in patients with type 2 diabetes mellitus. Int J Cardiol 2014; 172(1): e190-1.
[114]
Buraczynska M, Zukowski P, Drop B, Baranowicz-Gaszczyk I, Ksiazek A. Effect of G(-174)C polymorphism in interleukin-6 gene on cardiovascular disease in type 2 diabetes patients. Cytokine 2016; 79: 7-11.
[115]
Buraczynska M, Ksiazek K, Zukowski P, Grzebalska A. Interleukin-18 gene polymorphism and risk of CVD in older patients with type 2 diabetes mellitus. Diabetes Res Clin Pract 2016; 121: 178-83.
[116]
Biscetti F, Straface G, Bertoletti G, et al. Identification of a potential proinflammatory genetic profile influencing carotid plaque vulnerability. J Vasc Surg 2015; 61(2): 374-81.
[117]
Wu W, Wang M, Sun Z, Wang X, Miao J, Zheng Z. The predictive value of TNF-α and IL-6 and the incidence of macrovascular complications in patients with type 2 diabetes. Acta Diabetol 2012; 49(1): 3-7.
[118]
Gacka M, Dobosz T, Szymaniec S, Bednarska-Chabowska D, Adamiec R, Sadakierska-Chudy A. Proinflammatory and atherogenic activity of monocytes in type 2 diabetes. J Diabetes Complications 2010; 24(1): 1-8.
[119]
Terry CF, Loukaci V, Green FR. Cooperative influence of genetic polymorphisms on interleukin 6 transcriptional regulation. J Biol Chem 2000; 275(24): 18138-44.
[120]
Wilson AG, Symons JA, McDowell TL, McDevitt HO, Duff GW. Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. Proc Natl Acad Sci USA 1997; 94(7): 3195-9.
[121]
Vendrell J, Fernandez-Real JM, Gutierrez C, et al. A polymorphism in the promoter of the tumor necrosis factor-alpha gene (-308) is associated with coronary heart disease in type 2 diabetic patients. Atherosclerosis 2003; 167(2): 257-64.
[122]
Szabó GV, Acsády G. Tumornecrosis-factor-α 308 GA polymorphism in atherosclerotic patients. Pathol Oncol Res 2011; 17(4): 853-7.
[123]
Sobti RC, Kler R, Sharma YP, Talwar KK, Singh N. Risk of obesity and type 2 diabetes with tumor necrosis factor-α 308G/A gene polymorphism in metabolic syndrome and coronary artery disease subjects. Mol Cell Biochem 2012; 360(1-2): 1-7.
[124]
Guzmán-Flores JM, Muñoz-Valle JF, Sánchez-Corona J, et al. Tumor necrosis factor-alpha gene promoter -308G/A and -238G/A polymorphisms in Mexican patients with type 2 diabetes mellitus. Dis Markers 2011; 30(1): 19-24.
[125]
Luna GI, da Silva IC, Sanchez MN. Association between -308G/A TNFA polymorphism and susceptibility to type 2 diabetes mellitus: A systematic review. J Diabetes Res 2016; 2016: 6309484.
[126]
Rodrigues KF, Pietrani NT, Sandrim VC, et al. Association of a large panel of cytokine gene polymorphisms with complications and comorbidities in type 2 diabetes patients. J Diabetes Res 2015; 2015: 605965.
[127]
Sutton BS, Weinert S, Langefeld CD, et al. Genetic analysis of adiponectin and obesity in Hispanic families: The IRAS Family Study. Hum Genet 2005; 117(2-3): 107-18.
[128]
Mackevics V, Heid IM, Wagner SA, et al. The adiponectin gene is associated with adiponectin levels but not with characteristics of the insulin resistance syndrome in healthy Caucasians. Eur J Hum Genet 2006; 14(3): 349-56.
[129]
DeClercq V, Taylor C, Zahradka P. Adipose tissue: The link between obesity and cardiovascular disease. Cardiovasc Hematol Disord Drug Targets 2008; 8(3): 228-37.
[130]
Femia R, Kozakova M, Nannipieri M, et al. Carotid intima-media thickness in confirmed prehypertensive subjects: Predictors and progression. Arterioscler Thromb Vasc Biol 2007; 27(10): 2244-9.
[131]
Kim SH, Kang ES, Hur KY, et al. Adiponectin gene polymorphism 45T>G is associated with carotid artery plaques in patients with type 2 diabetes mellitus. Metabolism 2008; 57(2): 274-9.
[132]
Patel S, Flyvbjerg A, Kozàkovà M, et al. Variation in the ADIPOQ gene promoter is associated with carotid intima media thickness independent of plasma adiponectin levels in healthy subjects. Eur Heart J 2008; 29(3): 386-93.
[133]
Esteghamati A, Mansournia N, Nakhjavani M, Mansournia MA, Nikzamir A, Abbasi M. Association of +45(T/G) and +276(G/T) polymorphisms in the adiponectin gene with coronary artery disease in a population of Iranian patients with type 2 diabetes. Mol Biol Rep 2012; 39(4): 3791-7.
[134]
Kim SH, Kang ES, Hur KY, et al. Adiponectin gene polymorphism 45T>G is associated with carotid artery plaques in patients with type 2 diabetes mellitus. Metabolism 2008; 57(2): 274-9.
[135]
Nikolajević-Starčević J, Pleskovič A, Santl Letonja M, Jenko Pražnikar Z, Petrovič D. Polymorphisms +45T>G and +276G>T of the adiponectin gene does not affect plasma adiponectin level and carotid intima-media thickness in patients with diabetes mellitus type 2. Int Angiol 2014; 33(5): 434-40.
[136]
Gasbarrino K, Gorgui J, Nauche B, Côté R, Daskalopoulou SS. Circulating adiponectin and carotid intima-media thickness: A systematic review and meta-analysis. Metabolism 2016; 65(7): 968-86.
[137]
Martín-Timón I, Sevillano-Collantes C, Segura-Galindo A, Del Cañizo-Gómez FJ. Type 2 diabetes and cardiovascular disease: Have all risk factors the same strength? World J Diabetes 2014; 5(4): 444-70.
[138]
Popović D, Starčević JN, Letonja MS, et al. PECAM-1 gene polymorphism (rs668) and subclinical markers of carotid atherosclerosis in patients with type 2 diabetes mellitus. Balkan J Med Genet 2016; 19(1): 63-70.
[139]
Popović D, Starčević JN, Letonja MŠ, et al. Polymorphism rs5498 of the ICAM-1 gene affects the progression of carotid atherosclerosis in patients with type 2 diabetes mellitus. Lipids Health Dis 2016; 15: 79.
[140]
Helgadottir A, Thorleifsson G, Manolescu A, et al. A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science 2007; 316(5830): 1491-3.
[141]
McPherson R, Pertsemlidis A, Kavaslar N, et al. A common allele on chromosome 9 associated with coronary heart disease. Science 2007; 316(5830): 1488-91.
[142]
Samani NJ, Raitakari OT, Sipilä K, et al. Coronary artery disease-associated locus on chromosome 9p21 and early markers of atherosclerosis. Arterioscler Thromb Vasc Biol 2008; 28(9): 1679-83.
[143]
Wellcome Trust Case Control Consortium.Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 2007; 447(7145): 661-78.
[144]
Holdt LM, Teupser D. Recent studies of the human chromosome 9p21 locus, which is associated with atherosclerosis in human populations. Arterioscler Thromb Vasc Biol 2012; 32(2): 196-206.
[145]
Deloukas P, Kanoni S, Willenborg C, et al. Large-scale association analysis identifies new risk loci for coronary artery disease. Nat Genet 2013; 45(1): 25-33.
[147]
Zhang L, Buzkova P, Wassel CL, et al. Lack of associations of ten candidate coronary heart disease risk genetic variants and subclinical atherosclerosis in four US populations: The Population Architecture using Genomics and Epidemiology (PAGE) study. Atherosclerosis 2013; 228(2): 390-9.
[148]
Larson MG, Atwood LD, Benjamin EJ, et al. Framingham heart study 100K project: Genome-wide associations for cardiovascular disease outcomes. BMC Med Genet 2007; 8(Suppl. 1): 5.
[149]
O’Donnell CJ, Cupples LA, D’Agostino RB, et al. Genome-wide association study for subclinical atherosclerosis in major arterial territories in the NHLBI’s Framingham Heart Study. BMC Med Genet 2007; 8(Suppl. 1): 4.
[150]
Bis JC, Kavousi M, Franceschini N, et al. Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque. Nat Genet 2011; 43(10): 940-7.
[151]
Murabito JM, White CC, Kavousi M, et al. Association between chromosome 9p21 variants and the ankle-brachial index identified by a meta-analysis of 21 genome-wide association studies. Circ Cardiovasc Genet 2012; 5(1): 100-12.
[152]
Wild PS, Zeller T, Schillert A, et al. A genome-wide association study identifies LIPA as a susceptibility gene for coronary artery disease. Circ Cardiovasc Genet 2011; 4(4): 403-12.
[153]
Shrestha S, Irvin MR, Taylor KD, et al. A genome-wide association study of carotid atherosclerosis in HIV-infected men. AIDS 2010; 24(4): 583-92.
[154]
Sousa AG, Selvatici L, Krieger JE, Pereira AC. Association between genetics of diabetes, coronary artery disease, and macrovascular complications: Exploring a common ground hypothesis. Rev Diabet Stud 2011; 8(2): 230-44.
[155]
Qi Q, Meigs JB, Rexrode KM, Hu FB, Qi L. Diabetes genetic predisposition score and cardiovascular complications among patients with type 2 diabetes. Diabetes Care 2013; 36(3): 737-9.
[156]
Dauriz M, Meigs JB. Current insights into the joint genetic basis of type 2 diabetes and coronary heart disease. Curr Cardiovasc Risk Rep 2014; 8(1): 368.
Call for Papers in Thematic Issues
31 January, 2025
TREATMENT OF CARDIOVASCULAR DISEASE IN CHRONIC AND END STAGE KIDNEY DISEASE
Cardiovascular disease still remains the leading cause of death in Chronic and End Stage Kidney Disease, accounting for more than half of all deaths in dialysis patients. During the past decade, research has been focused on novel therapeutic agents that might delay or even reverse cardiovascular disease and vascular calcification, ...read more
Related Journals
Current Drug Safety
Current Cardiology Reviews
Cardiovascular & Hematological Agents in Medicinal Chemistry
Current Hypertension Reviews
Cardiovascular & Hematological Disorders-Drug Targets
Current Neuropharmacology
Current Pharmaceutical Design
Current Pharmaceutical Analysis
CNS & Neurological Disorders - Drug Targets
Current Molecular Pharmacology
Related Books
New Findings from Natural Substances
Pharmaceutical Chemistry and Production: An Introductory Textbook
Evidence-Based Research in Ayurveda against COVID-19 in Compliance with Standardized Protocols and Practices
Pharmaceuticals for Targeting Coronaviruses
Medical Applications of Beta-Glucan
Nanotechnology Driven Herbal Medicine for Burns: From Concept to Application
Herbal Medicine: Back to the Future
Cardiac Care and COVID-19: Perspectives in Medical Practice
Nanomedicinal Approaches Towards Cardiovascular Disease
Postbiotics: Science, Technology and Applications
Article Metrics
43
3