Abstract
Metabolic syndrome (MetS) is a risk factor for type 2 diabetes mellitus and cardiovascular disease. Obesity is a component of the metabolic syndrome. Several genetic variants are reported to be associated with obesity and hypo adiponectinemia, including ars1800796 polymorphism of the interleukin-6 (IL-6) gene. Since obesity is associated with inflammatory factors, the aim of this study was to investigate the association between this polymorphism and MetS and its related features. Obese patients with body mass index (BMI) ≥ 30 (n = 182) were recruited into this study and divided into two groups; 110 patients with MetS, based on the International Diabetes Federation (IDF) criteria, and 72 subjects without MetS. The anthropometric and biochemical data for the groups were compared. Genotyping was carried out using RT-PCR. The association of the genetic polymorphism with MetS and its components were assessed using univariate and multivariate analyzes. There was an association between the presence of the rs1800796polymorphism of the IL-6 gene, with BMI (P = 0.031), high-density lipoprotein (HDL) (P = 0.010) and low-density lipoprotein (LDL) (P = 0.037), while this genetic variant did not show any significant association with the presence of MetS as defined by the IDF. We demonstrate an association between the rs1800796 genetic variant of the IL-6 gene with components of MetS including BMI, and HDL-cholesterol, but not the MetS itself. Therefore, supporting further studies are warranted to investigate this point in a larger population.
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References
Abate M, Salini V, Andia I (2016) How obesity affects tendons? Adv Exp Med Biol 920:167–177
Ahmadnezhad M, Arefhosseini SR, Parizadeh MR, Tavallaie S, Tayefi M, Darroudi S et al (2018) Association between serum uric acid, high sensitive C-reactive protein and pro-oxidant-antioxidant balance in patients with metabolic syndrome. BioFactors 44:263
Alexopoulos AS, Fayfman M, Zhao L, Weaver J, Buehler L, Smiley D et al (2016) Impact of obesity on hospital complications and mortality in hospitalized patients with hyperglycemia and diabetes. BMJ Open Diabetes Res Care 4(1):e000200
Almeida DCd. Alterações genéticas relacionadas à obesidade: danos no DNA, perfil de expressão e polimorfismos gênicos. 2013.
Bagherniya M, Khayyatzadeh SS, Avan A, Safarian M, Nematy M, Ferns GA et al (2017) Metabolic syndrome and its components are related to psychological disorders: a population based study. Diabetes Metab Syndr 11(Suppl 2):S561–S566. https://doi.org/10.1016/j.dsx.2017.04.005
Bennet AM, Prince JA, Fei G-Z, Lyrenäs L, Huang Y, Wiman B et al (2003) Interleukin-6 serum levels and genotypes influence the risk for myocardial infarction. Atherosclerosis. 171(2):359–367
Bhatheja S, Panchal HB, Ventura H, Paul TK (2016) Obesity cardiomyopathy: pathophysiologic factors and nosologic reevaluation. Am J Med Sci 352(2):219–222
Chang W-T, Huang M-C, Chung H-F, Chiu Y-F, Chen P-S, Chen F-P et al (2016) Interleukin-6 gene polymorphisms correlate with the progression of nephropathy in Chinese patients with type 2 diabetes: a prospective cohort study. Diabetes Res Clin Pract 120:15–23
Dandona P, Aljada A, Bandyopadhyay A (2004) Inflammation: the link between insulin resistance, obesity and diabetes. Trends Immunol 25(1):4–7
Du Y, Gao L, Zhang K, Wang J (2015) Association of the IL6 polymorphism rs1800796 with cancer risk: a meta-analysis. Genet Mol Res. 14:13236–13246
Fernandes MT, Fernandes KB, Marquez AS, Cólus IM, Souza MF, Santos JPM et al (2015) Association of interleukin-6 gene polymorphism (rs1800796) with severity and functional status of osteoarthritis in elderly individuals. Cytokine 75(2):316–320
Ferrara N, Gerber H-P, LeCouter J (2003) The biology of VEGF and its receptors. Nat Med 9(6):669–676
Fragoso JM, Delgadillo H, Juárez-Cedillo T, Rodríguez-Pérez JM, Vallejo M, Pérez-Méndez O et al (2010) The interleukin 6–572 G%3e C (rs1800796) polymorphism is associated with the risk of developing acute coronary syndrome. Genet Test Mol Biomark 14(6):759–763
Galassi A, Reynolds K, He J (2006) Metabolic syndrome and risk of cardiovascular disease: a meta-analysis. Am J Med 119(10):812–819
Gato WE, Hunter DA, Whitby SL, Mays CA, Yau W (2016) Investigating susceptibility to diabetes using features of the adipose tissue in response to in utero polycyclic aromatic hydrocarbons exposure. Diabetes Metab J 46:494
Ghazizadeh H, Fazilati M, Pasdar A, Avan A, Tayefi M, Ghasemi F et al (2017) Association of a vascular endothelial growth factor genetic variant with serum VEGF level in subjects with metabolic syndrome. Gene 598:27–31
Ghazizadeh H, Avan A, Fazilati M, Azimi-Nezhad M, Tayefi M, Ghasemi F et al (2018) Association of rs6921438 A%3c G with serum vascular endothelial growth factor concentrations in patients with metabolic syndrome. Gene 667:70–75
Hamid Y, Rose C, Urhammer S, Glümer C, Nolsøe R, Kristiansen O et al (2005) Variations of the interleukin-6 promoter are associated with features of the metabolic syndrome in Caucasian Danes. Diabetologia 48(2):251–260
Hasnain S (2016) Obesity, more than a ‘cosmetic’problem Current knowledge and future prospects of human obesity genetics. Biochem Genet 54(1):1–28
Huth C, Heid IM, Vollmert C, Gieger C, Grallert H, Wolford JK et al (2006) IL6 gene promoter polymorphisms and type 2 diabetes joint analysis of individual participants’ data from 21 studies. Diabetes 55(10):2915–2921
Jeenduang N, Porntadavity S, Nuinoon M, Horpet D, Thepkwan N, Thaworn P et al (2015) Studies of the CETP TaqIB and ApoE polymorphisms in Southern Thai subjects with the metabolic syndrome. Biochem Genet 53(7–8):184–199
Karaman E, Kucuk MU, Bayramoglu A, Göçmen SU, Ercan S, Guler HI et al (2015) Investigation of relationship between IL-6 gene variants and hypertension in Turkish population. Cytotechnology 67(6):947–954
Lau C-H, Muniandy S (2013) Influence of adiponectin and resistin gene polymorphisms on quantitative traits related to metabolic syndrome among Malay, Chinese, and Indian men in Malaysia. Biochem Genet 51(1–2):166–174
Lubrano V, Gabriele M, Puntoni MR, Longo V, Pucci L (2015) Relationship among IL-6, LDL cholesterol and lipid peroxidation. Cell Mol Biol Lett 20(2):310–322
Matsui M, Takahashi Y, Takebe N, Takahashi K, Nagasawa K, Honma H et al (2015) Response to the dipeptidyl peptidase-4 inhibitors in Japanese patients with type 2 diabetes might be associated with a diplotype of two single nucleotide polymorphisms on the interleukin-6 promoter region under a certain level of physical activity. J Diabetes Investig 6(2):173–181
Mirhafez SR, Pasdar A, Avan A, Esmaily H, Moezzi A, Mohebati M et al (2015) Cytokine and growth factor profiling in patients with the metabolic syndrome. Br J Nutr 113(12):1911–1919
Mitrokhin V, Nikitin A, Brovkina O, Khodyrev D, Zotov A, Vachrushev N et al (2017) Association between interleukin-6/6R gene polymorphisms and coronary artery disease in Russian population: influence of interleukin-6/6R gene polymorphisms on inflammatory markers. J Inflam Res 10:151
Norde MM, Oki E, Carioca AAF, Damasceno NRT, Fisberg RM, Marchioni DML et al (2018) Influence of IL1B, IL6 and IL10 gene variants and plasma fatty acid interaction on metabolic syndrome risk in a cross-sectional population-based study. Clin Nutr 37(2):659–666
Park HS, Park JY, Yu R (2005) Relationship of obesity and visceral adiposity with serum concentrations of CRP, TNF-α and IL-6. Diabetes Res Clin Pract 69(1):29–35
Pérez AP, Munoz JY, Cortés VB, de Pablos Velasco P (2007) Obesity and cardiovascular disease. Public Health Nutr. 10(10A):1156–1163
Ponnana M, Sivangala R, Joshi L, Valluri V, Gaddam S (2017) IL-6 and IL-18 cytokine gene variants of pulmonary tuberculosis patients with co-morbid diabetes mellitus and their household contacts in Hyderabad. Gene 627:298–306
Rafiq S, Frayling T, Murray A, Hurst A, Stevens K, Weedon M et al (2007) A common variant of the interleukin 6 receptor (IL-6r) gene increases IL-6r and IL-6 levels, without other inflammatory effects. Genes Immun 8(7):552
Sirdah MM, Ghali ASA, Al Laham NA (2012) The reliability of the National Cholesterol Education Program's Adult Treatment Panel III (NCEP/ATP III) and the International Diabetes Federation (IDF) definitions in diagnosing metabolic syndrome (MetS) among Gaza Strip Palestinians. Diabetes Metab Syndr 6(1):4–8
Slattery ML, Wolff RK, Herrick JS, Caan BJ, Potter JD (2007) IL6 genotypes and colon and rectal cancer. Cancer Causes Control 18(10):1095–1105
Slattery ML, Curtin K, Sweeney C, Wolff RK, Baumgartner RN, Baumgartner KB et al (2008) Modifying effects of IL-6 polymorphisms on body size-associated breast cancer risk. Obesity. 16(2):339–347
Stephenson GD, Rose DP (2003) Breast cancer and obesity: an update. Nutr Cancer 45(1):1–16
Suazo J, Smalley S, Hodgson M, Weisstaub G, Gonzalez A, Santos J (2014) Association between genetic polymorphisms of interleukin 6 (IL6), IL6R and IL18 with metabolic syndrome in obese Chilean children. Rev Med Chil 142(3):290–298
Sun G, Wu G, Meng Y, Du B, Li Y (2014) IL-6 gene promoter polymorphisms and risk of coronary artery disease in a Chinese population. Genet Molec Res. 13:7718–7724
Sun H, Ren X, Chen Z, Li C, Chen S, Wu S et al (2016) Association between body mass index and mortality in a prospective cohort of Chinese adults. Medicine 95(32):e4327
Teixeira AA, Quinto BMR, Dalboni MA, Rodrigues CJdO, Batista MC (2015) Association of IL-6 polymorphism -174G/C and metabolic syndrome in hypertensive patients. BioMed Res Int 2015:6
Timasheva Y, Nasibullin T, Zakirova A, Mustafina O (2008) Association of interleukin-6, interleukin-12, and interleukin-10 gene polymorphisms with essential hypertension in Tatars from Russia. Biochem Genet 46(1–2):64–74
Underwood PC, Chamarthi B, Williams JS, Sun B, Vaidya A, Raby BA et al (2012) Replication and meta-analysis of the gene-environment interaction between body mass index and the interleukin-6 promoter polymorphism with higher insulin resistance. Metabolism. 61(5):667–671
Ururahy MAG, Souza KSC, Oliveira YMdC, Loureiro MB, Silva HPV, Freire-Neto FP et al (2015) Association of polymorphisms in IL6 gene promoter region with type 1 diabetes and increased albumin-to-creatinine ratio. Diabetes/Metab Res Rev 31(5):500–506
Wang Z, Wu S, Liao J, Zhong L, Xing T, Fan J et al (2016) Interleukin-6 and rs1800796 locus single nucleotide polymorphisms in response to hypoxia/reoxygenation in hepatocytes. Int J Mol Med 38(1):192–200
Zhang X, Liu R-Y, Lei Z, Zhu Y, Huang J-A, Jiang X et al (2009) Genetic variants in interleukin-6 modified risk of obstructive sleep apnea syndrome. Int J Mol Med 23(4):485
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This study was supported by a grant from Mashhad University of Medical Sciences.
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Barati, E., Ghazizadeh, H., Sadabadi, F. et al. Association of the IL6 Gene Polymorphism with Component Features of Metabolic Syndrome in Obese Subjects. Biochem Genet 57, 695–708 (2019). https://doi.org/10.1007/s10528-019-09913-5
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DOI: https://doi.org/10.1007/s10528-019-09913-5