Abstract
Polymorphisms in IL6, ACE and ATR genes are associated with obesity. Torque Teno virus (TTV) seems to be able to interfere with production of some proinflammatory cytokines associated with obesity and related phenotypes. The aim of this study was to test the potential association between obesity, TTV infection and the IL6 G-174C (rs1800795), ACE I/D (rs4646994), AT1R A1166C (rs5186) polymorphisms. The polymorphisms and the presence of TTV were detected in blood samples from 150 obese and 150 normal-weight, healthy subjects using PCR based methods. IL6-174 CC genotype was more frequent in all obese patients (P=0.02) and in patients without TTV infections (P=0.03) than in controls. Obese women had more frequent TTV infections compared with normal-weight women (P=0.046). Obese subjects, regardless of gender (women P=0.03, men P=0.04), and healthy normal-weight men (P<0.01) carriers of AT1R C allele had higher triglycerides levels compared with non-carriers. The frequency of TTV in the control group (70.67%) was similar to data reported in other populations. The present study indicated that IL6-174 CC genotype and TTV infections in women could be associated with the common form of obesity.
Similar content being viewed by others
References
Pasarica M., Dhurandhar N.V., Infectobesity: obesity of infectious origin, Adv. Food. Nutr. Res., 2007, 52, 61–102
Cousin B., Munoz O., Andre M., Fontanilles A.M., Dani C., Cousin J.L., et al., A role for preadipocytes as macrophage-like cells, FASEB J., 1999, 13, 305–312
Levitan R.D., Masellis M., Lam R.W., Kaplan A.S., Davis C., Tharmalingam S., et al., A birthseason/DRD4 gene interaction predicts weight gain and obesity in women with seasonal affective disorder: A seasonal thrifty phenotype hypothesis, Neuropsychopharmacology, 2006, 31, 2498–2503
Phillips D.I., Young J.B., Birth weight, climate at birth and the risk of obesity in adult life, Int. J. Obes. Relat. Metab. Disord., 2000, 24, 281–287
van Ginneken V., Sitnyakowsky L., Jeffery J.E., Infectobesity: viral infections (especially with human adenovirus-36: Ad-36) may be a cause of obesity, Med. Hypotheses., 2009, 72, 383–388
Nishizawa T., Okamoto H., Konishi K., Yoshizawa H., Miyakawa Y., Mayumi M., A novel DNA virus (TTV) associated with elevated transaminase levels in posttransfusion hepatitis of unknown etiology, Biochem. Biophys. Res. Commun., 1997, 241, 92–97
Pollicino T., Raffa G., Squadrito G., Costantino L., Cacciola I., Brancatelli S., et al., TT virus has a ubiquitous diffusion in human body tissues: analyses of paired serum and tissue samples, J. Viral. Hepat., 2003, 10, 95–102
Eder K., Baffy N., Falus A., Fulop A.K., The major inflammatory mediator interleukin-6 and obesity, Inflamm. Res., 2009, 58, 727–736
Qi L., Zhang C., van Dam R.M., Hu F.B., Interleukin-6 genetic variability and adiposity: associations in two prospective cohorts and systematic review in 26,944 individuals, J. Clin. Endocrinol. Metab., 2007, 92, 3618–3625
Stelzer I., Zelzer S., Raggam R.B., Pruller F., Truschnig-Wilders M., Meinitzer A., et al., Link between leptin and interleukin-6 levels in the initial phase of obesity related inflammation, Transl. Res., 2012, 159, 118–124
Berthier M.T., Paradis A.M., Tchernof A., Bergeron J., Prud’homme D., Despres J.P., et al., The interleukin 6–174G/C polymorphism is associated with indices of obesity in men, J. Hum. Genet., 2003, 48, 14–19
Klipstein-Grobusch K., Mohlig M., Spranger J., Hoffmann K., Rodrigues F.U., Sharma A.M., et al., Interleukin-6 g.-174G>C promoter polymorphism is associated with obesity in the EPIC-Potsdam Study, Obesity (Silver Spring), 2006, 14, 14–18
Moffett S.P., Zmuda J.M., Cauley J.A., Stone K.L., Nevitt M.C., Ensrud K.E., et al., Association of the G-174C variant in the interleukin-6 promoter region with bone loss and fracture risk in older women, J. Bone. Miner. Res., 2004, 19, 1612–1618
Stephens J.W., Hurel S.J., Cooper J.A., Acharya J., Miller G.J., Humphries S.E., A common functional variant in the interleukin-6 gene is associated with increased body mass index in subjects with type 2 diabetes mellitus, Mol. Genet. Metab., 2004, 82, 180–186
Wernstedt I., Eriksson A.L., Berndtsson A., Hoffstedt J., Skrtic S., Hedner T., et al., A common polymorphism in the interleukin-6 gene promoter is associated with overweight, Int. J. Obes. Relat. Metab. Disord., 2004, 28, 1272–1279
Bennermo M., Held C., Stemme S., Ericsson C.G., Silveira A., Green F., et al., Genetic predisposition of the interleukin-6 response to inflammation: implications for a variety of major diseases?, Clin. Chem., 2004, 50, 2136–2140
Schling P., Mallow H., Trindl A., Loffler G., Evidence for a local renin angiotensin system in primary cultured human preadipocytes, Int. J. Obes. Relat. Metab. Disord., 1999, 23, 336–341
Engeli S., Gorzelniak K., Kreutz R., Runkel N., Distler A., Sharma A.M., Co-expression of reninangiotensin system genes in human adipose tissue, J. Hypertens., 1999, 17, 555–560
Phillips M.I., Kagiyama S., Angiotensin II as a proinflammatory mediator, Curr. Opin. Investig. Drugs, 2002, 3, 569–577
de Kloet A.D., Krause E.G., Woods S.C., The renin angiotensin system and the metabolic syndrome, Physiol. Behav., 2010, 100, 525–534
Goossens G.H., Blaak E.E., van Baak M.A., Possible involvement of the adipose tissue reninangiotensin system in the pathophysiology of obesity and obesity-related disorders, Obes. Rev., 2003, 4, 43–55
Nickenig G., Roling J., Strehlow K., Schnabel P., Bohm M., Insulin induces upregulation of vascular AT1 receptor gene expression by posttranscriptional mechanisms, Circulation, 1998, 98, 2453–2460
Barton M., Carmona R., Ortmann J., Krieger J.E., Traupe T., Obesity-associated activation of angiotensin and endothelin in the cardiovascular system, Int. J. Biochem. Cell Biol., 2003, 35, 826–837
Ye S., Dhillon S., Ke X., Collins A.R., Day I.N., An efficient procedure for genotyping single nucleotide polymorphisms, Nucleic Acids Res., 2001, 29, E88–88
Tiret L., Rigat B., Visvikis S., Breda C., Corvol P., Cambien F., et al., Evidence, from combined segregation and linkage analysis, that a variant of the angiotensin I-converting enzyme (ACE) gene controls plasma ACE levels, Am. J. Hum. Genet., 1992, 51, 197–205
Doria A., Ji L., Warram J.H., Krolewski A.S., DdeI polymorphism in the AGTR1 gene, Hum. Mol. Genet., 1994, 3, 1444
Lindpaintner K., Pfeffer M.A., Kreutz R., Stampfer M.J., Grodstein F., LaMotte F., et al., A prospective evaluation of an angiotensin-converting-enzyme gene polymorphism and the risk of ischemic heart disease, N. Engl. J. Med., 1995, 332, 706–711
Ninomiya M., Takahashi M., Nishizawa T., Shimosegawa T., Okamoto H., Development of PCR assays with nested primers specific for differential detection of three human anelloviruses and early acquisition of dual or triple infection during infancy, J. Clin. Microbiol., 2008, 46, 507–514
Schoonjans F., Zalata A., Depuydt C.E., Comhaire F.H., MedCalc: a new computer program for medical statistics, Comput. Methods Programs Biomed., 1995, 48, 257–262
Terry C.F., Loukaci V., Green F.R., Cooperative influence of genetic polymorphisms on interleukin 6 transcriptional regulation, J. Biol. Chem., 2000, 275, 18138–18144
Yang X., Jansson P.A., Pellme F., Laakso M., Smith U., Effect of the interleukin-6 (−174) g/c promoter polymorphism on adiponectin and insulin sensitivity, Obes. Res., 2005, 13, 813–817
van Geel P.P., Pinto Y.M., Voors A.A., Buikema H., Oosterga M., Crijns H.J., et al., Angiotensin II type 1 receptor A1166C gene polymorphism is associated with an increased response to angiotensin II in human arteries, Hypertension, 2000, 35, 717–721
Zheng H., Ye L., Fang X., Li B., Wang Y., Xiang X., et al., Torque teno virus (SANBAN isolate) ORF2 protein suppresses NF-kappaB pathways via interaction with IkappaB kinases, J. Virol., 2007, 81, 11917–11924
Batra A., Pietsch J., Fedke I., Glauben R., Okur B., Stroh T., et al., Leptin-dependent toll-like receptor expression and responsiveness in preadipocytes and adipocytes, Am. J. Pathol., 2007, 170, 1931–1941
Rocchi J., Ricci V., Albani M., Lanini L., Andreoli E., Macera L., et al., Torquetenovirus DNA drives proinflammatory cytokines production and secretion by immune cells via toll-like receptor 9, Virology, 2009, 394, 235–242
Yokoyama H., Yasuda J., Okamoto H., Iwakura Y., Pathological changes of renal epithelial cells in mice transgenic for the TT virus ORF1 gene, J. Gen. Virol., 2002, 83, 141–150
De Benedetti F., Alonzi T., Moretta A., Lazzaro D., Costa P., Poli V., et al., Interleukin 6 causes growth impairment in transgenic mice through a decrease in insulin-like growth factor-I. A model for stunted growth in children with chronic inflammation, J. Clin. Invest., 1997, 99, 643–650
Barker D.J., Eriksson J.G., Forsen T., Osmond C., Fetal origins of adult disease: strength of effects and biological basis, Int. J. Epidemiol., 2002, 31, 1235–1239
Fried S.K., Bunkin D.A., Greenberg A.S., Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid, J. Clin. Endocrinol. Metab., 1998, 83, 847–850
Fain J.N., Madan A.K., Hiler M.L., Cheema P., Bahouth S.W., Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans, Endocrinology, 2004, 145, 2273–2282
Fain J.N., Release of interleukins and other inflammatory cytokines by human adipose tissue is enhanced in obesity and primarily due to the nonfat cells, Vitam. Horm., 2006, 74, 443–477
Rexrode K.M., Pradhan A., Manson J.E., Buring J.E., Ridker P.M., Relationship of total and abdominal adiposity with CRP and IL-6 in women, Ann. Epidemiol., 2003, 13, 674–682
Vozarova B., Weyer C., Hanson K., Tataranni P.A., Bogardus C., Pratley R.E., Circulating interleukin-6 in relation to adiposity, insulin action, and insulin secretion, Obes. Res., 2001, 9, 414–417
Manco M., Fernandez-Real J.M., Equitani F., Vendrell J., Valera Mora M.E., Nanni G., et al., Effect of massive weight loss on inflammatory adipocytokines and the innate immune system in morbidly obese women, J. Clin. Endocrinol. Metab., 2007, 92, 483–490
Wisse B.E., The inflammatory syndrome: the role of adipose tissue cytokines in metabolic disorders linked to obesity, J. Am. Soc. Nephrol., 2004, 15, 2792–2800
van Hall G., Steensberg A., Sacchetti M., Fischer C., Keller C., Schjerling P., et al., Interleukin-6 stimulates lipolysis and fat oxidation in humans, J. Clin. Endocrinol. Metab., 2003, 88, 3005–3010
Trujillo M.E., Sullivan S., Harten I., Schneider S.H., Greenberg A.S., Fried S.K., Interleukin-6 regulates human adipose tissue lipid metabolism and leptin production in vitro, J. Clin. Endocrinol. Metab., 2004, 89, 5577–5582
Path G., Bornstein S.R., Gurniak M., Chrousos G.P., Scherbaum W.A., Hauner H., Human breast adipocytes express interleukin-6 (IL-6) and its receptor system: increased IL-6 production by beta-adrenergic activation and effects of IL-6 on adipocyte function, J. Clin. Endocrinol. Metab., 2001, 86, 2281–2288
Plata-Salaman C.R., Immunoregulators in the nervous system, Neurosci. Biobehav. Rev., 1991, 15, 185–215
Wallenius V., Wallenius K., Ahren B., Rudling M., Carlsten H., Dickson S.L., et al., Interleukin-6-deficient mice develop mature-onset obesity, Nat. Med., 2002, 8, 75–79
Fishman D., Faulds G., Jeffery R., Mohamed-Ali V., Yudkin J.S., Humphries S., et al., The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis, J. Clin. Invest., 1998, 102, 1369–1376
Ray A., Tatter S.B., May L.T., Sehgal P.B., Activation of the human “beta 2-interferon/hepatocytestimulating factor/interleukin 6” promoter by cytokines, viruses, and second messenger agonists, Proc. Natl. Acad. Sci. U S A, 1988, 85, 6701–6705
Isshiki H., Akira S., Tanabe O., Nakajima T., Shimamoto T., Hirano T., et al., Constitutive and interleukin-1 (IL-1)-inducible factors interact with the IL-1-responsive element in the IL-6 gene, Mol. Cell. Biol., 1990, 10, 2757–2764
Kopf M., Baumann H., Freer G., Freudenberg M., Lamers M., Kishimoto T., et al., Impaired immune and acute-phase responses in interleukin-6-deficient mice, Nature, 1994, 368, 339–342
Kopf M., Ramsay A., Brombacher F., Baumann H., Freer G., Galanos C., et al., Pleiotropic defects of IL-6-deficient mice including early hematopoiesis, T and B cell function, and acute phase responses, Ann. N Y Acad. Sci., 1995, 308–318
Vasilyev E.V., Trofimov D.Y., Tonevitsky A.G., Ilinsky V.V., Korostin D.O., Rebrikov D.V., Torque Teno Virus (TTV) distribution in healthy Russian population, Virol. J., 2009, 6, 134–138
Urwijitaroon Y., Barusrux S., Chunlertlith K., Mairiang P., Yoshimura H., Torquetenovirus infection among northeastern Thai blood donors, Southeast Asian J. Trop. Med. Public Health, 2007, 38, 686–689
Al-Moslih M.I., Abuodeh R.O., Hu Y.W., Detection and genotyping of TT virus in healthy and subjects with HBV or HCV in different populations in the United Arab Emirates, J. Med. Virol., 2004, 72, 502–508
Odemis E., Gurakan F., Ergunay K., Yuce A., Ozen H., Kocak N., TTV infection in children with and without liver disease, Indian J. Gastroenterol., 2004, 23, 135–137
Thomas G.N., Tomlinson B., Chan J.C., Sanderson J.E., Cockram C.S., Critchley J.A., Reninangiotensin system gene polymorphisms, blood pressure, dyslipidemia, and diabetes in Hong Kong Chinese: a significant association of tne ACE insertion/deletion polymorphism with type 2 diabetes, Diabetes Care, 2001, 24, 356–361
Kim K., Association of angiotensin-converting enzyme insertion/deletion polymorphism with obesity, cardiovascular risk factors and exercisemediated changes in Korean women, Eur. J. Appl. Physiol., 2009, 105, 879–887
Alavi-Shahri J., Behravan J., Hassany M., Tatari F., Kasaian J., Ganjali R., et al., Association between angiotensin II type 1 receptor gene polymorphism and metabolic syndrome in a young female Iranian population, Arch. Med. Res., 2010, 41, 343–349
Manea S.A., Robciuc A., Guja C., Heltianu C., Identification of gene variants in NOS3, ET-1 and RAS that confer risk and protection against microangiopathy in type 2 diabetic obese subjects, Biochem. Biophys. Res. Commun., 2011, 407, 486–490
Eisenmann J.C., Sarzynski M.A., Glenn K., Rothschild M., Heelan K.A., ACE I/D genotype, adiposity, and blood pressure in children, Cardiovasc. Diabetol., 2009, 8, 14–22
Lagou V., Manios Y., Moran C.N., Bailey M.E., Grammatikaki E., Oikonomou E., et al., Developmental changes in adiposity in toddlers and preschoolers in the GENESIS study and associations with the ACE I/D polymorphism, Int. J. Obes. (Lond.), 2007, 31, 1052–1060
Strazzullo P., Iacone R., Iacoviello L., Russo O., Barba G., Russo P., et al., Genetic variation in the renin-angiotensin system and abdominal adiposity in men: the Olivetti Prospective Heart Study, Ann. Intern. Med., 2003, 138, 17–23
Abdollahi M.R., Gaunt T.R., Syddall H.E., Cooper C., Phillips D.I., Ye S., et al., Angiotensin II type I receptor gene polymorphism: anthropometric and metabolic syndrome traits, J. Med. Genet., 2005, 42, 396–401
Niel C., de Oliveira J.M., Ross R.S., Gomes S.A., Roggendorf M., Viazov S., High prevalence of TT virus infection in Brazilian blood donors, J. Med. Virol., 1999, 57, 259–263
Maggi F., Andreoli E., Lanini L., Fornai C., Vatteroni M., Pistello M., et al., Relationships between total plasma load of torquetenovirus (TTV) and TTV genogroups carried, J. Clin. Microbiol., 2005, 43, 4807–4810
Parra-Rojas I., Ruiz-Madrigal B., Martinez-Lopez E., Panduro A., Influence of the −308 TNF-alpha and −174 IL-6 polymorphisms on lipid profile in Mexican subjects, Hereditas, 2006, 143, 167–172
Comas D., Schmid H., Braeuer S., Flaiz C., Busquets A., Calafell F., et al., Alu insertion polymorphisms in the Balkans and the origins of the Aromuns, Ann. Hum. Genet., 2004, 68, 120–127
Thameem F., Voruganti V.S., He X., Nath S.D., Blangero J., MacCluer J.W., et al., Genetic variants in the renin-angiotensin system genes are associated with cardiovascular-renal-related risk factors in Mexican Americans, Hum. Genet., 2008, 124, 557–559
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Cimponeriu, D., Serafinceanu, C., Apostol, P. et al. Potential association of obesity with IL6 G-174C polymorphism and TTV infections. cent.eur.j.biol. 8, 625–632 (2013). https://doi.org/10.2478/s11535-013-0178-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.2478/s11535-013-0178-1