Association of adiponectin (ADIPOQ) rs2241766 polymorphism and dyslipidemia in HIV/HCV-coinfected patients
Daniel Pineda-Tenor
Viral Infection and Immunity Unit, National Centre of Microbiology, Instituto de Salud Carlos III, Madrid, Spain
Search for more papers by this authorJuan Berenguer
Infectious Diseases-HIV Unit, Hospital General Universitario “Gregorio Marañón”, Madrid, Spain
Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
Search for more papers by this authorPilar García-Broncano
Viral Infection and Immunity Unit, National Centre of Microbiology, Instituto de Salud Carlos III, Madrid, Spain
Search for more papers by this authorMaría A. Jiménez-Sousa
Viral Infection and Immunity Unit, National Centre of Microbiology, Instituto de Salud Carlos III, Madrid, Spain
Search for more papers by this authorAmanda Fernández-Rodríguez
Viral Infection and Immunity Unit, National Centre of Microbiology, Instituto de Salud Carlos III, Madrid, Spain
Search for more papers by this authorCristina Diez
Infectious Diseases-HIV Unit, Hospital General Universitario “Gregorio Marañón”, Madrid, Spain
Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
Search for more papers by this authorMónica García–Álvarez
Viral Infection and Immunity Unit, National Centre of Microbiology, Instituto de Salud Carlos III, Madrid, Spain
Search for more papers by this authorAna Carrero
Infectious Diseases-HIV Unit, Hospital General Universitario “Gregorio Marañón”, Madrid, Spain
Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
Search for more papers by this authorPilar Catalán
Microbiology Department, Hospital General Universitario “Gregorio Marañón”, Madrid, Spain
Search for more papers by this authorTeresa Aldámiz-Echevarria
Infectious Diseases-HIV Unit, Hospital General Universitario “Gregorio Marañón”, Madrid, Spain
Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
Search for more papers by this authorCorresponding Author
Salvador Resino
Viral Infection and Immunity Unit, National Centre of Microbiology, Instituto de Salud Carlos III, Madrid, Spain
Correspondence to: Salvador Resino; Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda); Carretera Majadahonda- Pozuelo, Km 2·2; 28220 Majadahonda, Madrid, Spain. Tel.: +34 918 223 266; fax: +34 918 223 269; e-mail: [email protected]Search for more papers by this authorDaniel Pineda-Tenor
Viral Infection and Immunity Unit, National Centre of Microbiology, Instituto de Salud Carlos III, Madrid, Spain
Search for more papers by this authorJuan Berenguer
Infectious Diseases-HIV Unit, Hospital General Universitario “Gregorio Marañón”, Madrid, Spain
Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
Search for more papers by this authorPilar García-Broncano
Viral Infection and Immunity Unit, National Centre of Microbiology, Instituto de Salud Carlos III, Madrid, Spain
Search for more papers by this authorMaría A. Jiménez-Sousa
Viral Infection and Immunity Unit, National Centre of Microbiology, Instituto de Salud Carlos III, Madrid, Spain
Search for more papers by this authorAmanda Fernández-Rodríguez
Viral Infection and Immunity Unit, National Centre of Microbiology, Instituto de Salud Carlos III, Madrid, Spain
Search for more papers by this authorCristina Diez
Infectious Diseases-HIV Unit, Hospital General Universitario “Gregorio Marañón”, Madrid, Spain
Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
Search for more papers by this authorMónica García–Álvarez
Viral Infection and Immunity Unit, National Centre of Microbiology, Instituto de Salud Carlos III, Madrid, Spain
Search for more papers by this authorAna Carrero
Infectious Diseases-HIV Unit, Hospital General Universitario “Gregorio Marañón”, Madrid, Spain
Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
Search for more papers by this authorPilar Catalán
Microbiology Department, Hospital General Universitario “Gregorio Marañón”, Madrid, Spain
Search for more papers by this authorTeresa Aldámiz-Echevarria
Infectious Diseases-HIV Unit, Hospital General Universitario “Gregorio Marañón”, Madrid, Spain
Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
Search for more papers by this authorCorresponding Author
Salvador Resino
Viral Infection and Immunity Unit, National Centre of Microbiology, Instituto de Salud Carlos III, Madrid, Spain
Correspondence to: Salvador Resino; Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda); Carretera Majadahonda- Pozuelo, Km 2·2; 28220 Majadahonda, Madrid, Spain. Tel.: +34 918 223 266; fax: +34 918 223 269; e-mail: [email protected]Search for more papers by this authorAbstract
Background
The adiponectin (ADIPOQ) rs2241766 polymorphism is related to metabolic abnormalities. The aim of this study was to evaluate the association of the ADIPOQ rs2241766 polymorphism with serum dyslipidemia and insulin resistance (IR) in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients.
Methods
We carried out a cross-sectional study on 262 patients. ADIPOQ rs2241766 polymorphisms were genotyped by GoldenGate® assay. Generalized linear models (GLMs) were used to compare continuous outcome variables (total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C and homeostatic model assessment (HOMA)) and categorical outcome variables (TC ≥ 200 mg/dL, TG ≥ 170 mg/dL, LDL-C ≥ 100 mg/dL, HDL-C ≤ 35 mg/dL, non-HDL-C ≥ 120 mg/dL and HOMA ≥ 3·8) according to ADIPOQ genotype under a dominant inheritance model.
Results
Patients with the rs2241766 GG/GT genotype had significantly lower serum TC levels (P = 0·038) and percentages of TC ≥ 200 mg/dL (P = 0·022) than rs2241766 TT carriers. When adjusted GLM was performed, rs2241766 GG/GT was associated with low serum TC levels (arithmetic mean ratio (AMR) = 0·92 [(95% CI = 0·85; 0·99) P = 0·024]) and low likelihood of TC ≥ 200 mg/dL (odds ratio (OR) = 0·32 [(95% CI = 0·11; 0·88) P = 0·027]. When stratifying by steatosis, no significant values were found for patients without steatosis. However, for patients with steatosis, rs2241766 GG/GT genotypes were related to low TC serum values of TC (AMR = 0·89; P = 0·027), LDL-C (AMR = 0·85; P = 0·039) and non-HDL-C (AMR = 0·86; P = 0·015). No significant associations were found between rs2241766 and HOMA values.
Conclusions
The presence of the ADIPOQ rs2241766 G allele (GG/GT genotype) was associated with a protective effect against dyslipidemia, primarily in HIV/HCV-coinfected patients with steatosis.
Supporting Information
| Filename | Description |
|---|---|
| eci12250-sup-0001-FigS1-S2-TableS1.docxWord document, 69.4 KB | Figure S1. Distribution of HOMA values and insulin resistance according to ADIPOQ rs2241766 polymorphism and stratified by liver fibrosis in HIV/HCV-coinfected patients. Figure S2. Association of ADIPOQ rs2241766 polymorphism with HOMA (a) and insulin resistance (HOMA ≥ 3·8) (b) by generalized linear model (GLM) tests in HIV/HCV-coinfected patients. Table S1. Estimation of statistical power performed a posteriori for two independent groups (http://www.imim.cat/ofertadeserveis/software-public/granmo/), in those cases where the statistical significance was found. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1Samaras K. Metabolic consequences and therapeutic options in highly active antiretroviral therapy in human immunodeficiency virus-1 infection. J Antimicrob Chemother 2008; 61: 238–45.
- 2Calza L, Manfredi R, Pocaterra D, Chiodo F. Risk of premature atherosclerosis and ischemic heart disease associated with HIV infection and antiretroviral therapy. J Infect 2008; 57: 16–32.
- 3Triant VA, Lee H, Hadigan C, Grinspoon SK. Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease. J Clin Endocrinol Metab 2007; 92: 2506–12.
- 4Negro F, Sanyal AJ. Hepatitis C virus, steatosis and lipid abnormalities: clinical and pathogenic data. Liver Int 2009; 29(Suppl 2): 26–37.
- 5Younossi ZM, McCullough AJ. Metabolic syndrome, non-alcoholic fatty liver disease and hepatitis C virus: impact on disease progression and treatment response. Liver Int 2009; 29(Suppl 2): 3–12.
- 6Younossi ZM, Stepanova M, Nader F, Younossi Z, Elsheikh E. Associations of chronic hepatitis C with metabolic and cardiac outcomes. Aliment Pharmacol Ther 2013; 37: 647–52.
- 7Lopez-Dieguez M, Montes ML, Pascual-Pareja JF, Quereda C, Von Wichmann MA, Berenguer J et al. The natural history of liver cirrhosis in HIV-hepatitis C virus-coinfected patients. AIDS 2011; 25: 899–904.
- 8Macias J, Berenguer J, Japon MA, Giron JA, Rivero A, Lopez-Cortes LF et al. Fast fibrosis progression between repeated liver biopsies in patients coinfected with human immunodeficiency virus/hepatitis C virus. Hepatology 2009; 50: 1056–63.
- 9Bedimo R, Westfall AO, Mugavero M, Drechsler H, Khanna N, Saag M. Hepatitis C virus coinfection and the risk of cardiovascular disease among HIV-infected patients. HIV Med 2010; 11: 462–8.
- 10Kotler DP. Hepatitis C human immunodeficiency virus and metabolic syndrome: interactions. Liver Int 2009; 29(Suppl 2): 38–46.
- 11Sahin-Efe A, Katsikeris F, Mantzoros CS. Advances in adipokines. Metabolism 2012; 61: 1659–65.
- 12Martin LJ, Woo JG, Daniels SR, Goodman E, Dolan LM. The relationships of adiponectin with insulin and lipids are strengthened with increasing adiposity. J Clin Endocrinol Metab 2005; 90: 4255–9.
- 13Scherer PE. Adipose tissue: from lipid storage compartment to endocrine organ. Diabetes 2006; 55: 1537–45.
- 14Bremer AA, Jialal I. Adipose tissue dysfunction in nascent metabolic syndrome. J Obes 2013; 2013: 393192.
- 15Xu A, Wang Y, Keshaw H, Xu LY, Lam KS, Cooper GJ. The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice. J Clin Invest 2003; 112: 91–100.
- 16Bastard JP, Maachi M, Lagathu C, Kim MJ, Caron M, Vidal H et al. Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw 2006; 17: 4–12.
- 17Bertolani C, Marra F. Role of adipocytokines in hepatic fibrosis. Curr Pharm Des 2010; 16: 1929–40.
- 18Grigorescu M, Radu C, Crisan D, Grigorescu MD, Serban A, Neculoiu D et al. Metabolic syndrome, insulin resistance and adiponectin level in patients with chronic hepatitis C. J Gastrointestin Liver Dis 2008; 17: 147–54.
- 19Fukushima N, Kuromatsu R, Arinaga-Hino T, Ando E, Takata A, Sumie S et al. Adipocytokine involvement in hepatocellular carcinoma after sustained response to interferon for chronic hepatitis C. Hepatol Res 2010; 40: 911–22.
- 20Heid IM, Wagner SA, Gohlke H, Iglseder B, Mueller JC, Cip P et al. Genetic architecture of the APM1 gene and its influence on adiponectin plasma levels and parameters of the metabolic syndrome in 1,727 healthy Caucasians. Diabetes 2006; 55: 375–84.
- 21Zhang H, Mo X, Hao Y, Gu D. Association between polymorphisms in the adiponectin gene and cardiovascular disease: a meta-analysis. BMC Med Genet 2012; 13: 40.
- 22Han LY, Wu QH, Jiao ML, Hao YH, Liang LB, Gao LJ et al. Associations between single-nucleotide polymorphisms (+45T>G, +276G>T, -11377C>G, -11391G>A) of adiponectin gene and type 2 diabetes mellitus: a systematic review and meta-analysis. Diabetologia 2011; 54: 2303–14.
- 23Zhao T, Zhao J. Genetic effects of adiponectin on blood lipids and blood pressure. Clin Endocrinol (Oxf) 2011; 74: 214–22.
- 24Simera I, Moher D, Hoey J, Schulz KF, Altman DG. A catalogue of reporting guidelines for health research. Eur J Clin Invest 2010; 40: 35–53.
- 25Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499–502.
- 26Martinez-Hervas S, Real JT, Priego MA, Carratala A, Sniderman AD, Carmena R et al. Establishing cut-off values for apolipoprotein B and non-HDL-C according to LDL-C values in a South European population. Int J Clin Pract 2013; 67: 81–8.
- 27Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412–9.
- 28Jacobs WH, Goldberg SB. Statement on outpatient percutaneous liver biopsy. Dig Dis Sci 1989; 34: 322–3.
- 29Eslam M, Kawaguchi T, Del Campo JA, Sata M, Khattab MA, Romero-Gomez M. Use of HOMA-IR in hepatitis C. J Viral Hepat 2011; 18: 675–84.
- 30Bersot TP, Pepin GM, Mahley RW. Risk determination of dyslipidemia in populations characterized by low levels of high-density lipoprotein cholesterol. Am Heart J 2003; 146: 1052–9.
- 31Lindsey JK, Jones B. Choosing among generalized linear models applied to medical data. Stat Med 1998; 17: 59–68.
10.1002/(SICI)1097-0258(19980115)17:1<59::AID-SIM733>3.0.CO;2-7 CAS PubMed Web of Science® Google Scholar
- 32Cesari M, Narkiewicz K, De Toni R, Aldighieri E, Williams CJ, Rossi GP. Heritability of plasma adiponectin levels and body mass index in twins. J Clin Endocrinol Metab 2007; 92: 3082–8.
- 33Mackevics V, Heid IM, Wagner SA, Cip P, Doppelmayr H, Lejnieks A 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: 349–56.
- 34Berthier MT, Houde A, Cote M, Paradis AM, Mauriege P, Bergeron J et al. Impact of adiponectin gene polymorphisms on plasma lipoprotein and adiponectin concentrations of viscerally obese men. J Lipid Res 2005; 46: 237–44.
- 35Menzaghi C, Trischitta V, Doria A. Genetic influences of adiponectin on insulin resistance, type 2 diabetes, and cardiovascular disease. Diabetes 2007; 56: 1198–209.
- 36Al-Daghri NM, Al-Attas OS, Alokail MS, Alkharfy KM, Hussain T, Yakout S et al. Adiponectin gene polymorphisms (T45G and G276T), adiponectin levels and risk for metabolic diseases in an Arab population. Gene 2012; 493: 142–7.
- 37Antonopoulos AS, Tousoulis D, Antoniades C, Miliou A, Hatzis G, Papageorgiou N et al. Genetic variability on adiponectin gene affects myocardial infarction risk: The role of endothelial dysfunction. Int J Cardiol 2013; 168: 326–30.
- 38Asselbergs FW, Guo Y, van Iperen EP, Sivapalaratnam S, Tragante V, Lanktree MB et al. Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci. Am J Hum Genet 2012; 91: 823–38.
- 39Morris AP, Voight BF, Teslovich TM, Ferreira T, Segre AV, Steinthorsdottir V et al. Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nat Genet 2012; 44: 981–90.
- 40Manning AK, Hivert MF, Scott RA, Grimsby JL, Bouatia-Naji N, Chen H et al. A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance. Nat Genet 2012; 44: 659–69.
- 41Kraja AT, Vaidya D, Pankow JS, Goodarzi MO, Assimes TL, Kullo IJ et al. A bivariate genome-wide approach to metabolic syndrome: STAMPEED consortium. Diabetes 2011; 60: 1329–39.
- 42Gable DR, Hurel SJ, Humphries SE. Adiponectin and its gene variants as risk factors for insulin resistance, the metabolic syndrome and cardiovascular disease. Atherosclerosis 2006; 188: 231–44.
- 43Hara K, Boutin P, Mori Y, Tobe K, Dina C, Yasuda K et al. Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population. Diabetes 2002; 51: 536–40.
- 44Siitonen N, Pulkkinen L, Lindstrom J, Kolehmainen M, Eriksson JG, Venojarvi M et al. Association of ADIPOQ gene variants with body weight, type 2 diabetes and serum adiponectin concentrations: the Finnish Diabetes Prevention Study. BMC Med Genet 2011; 12: 5.
- 45Ukkola O, Ravussin E, Jacobson P, Sjostrom L, Bouchard C. Mutations in the adiponectin gene in lean and obese subjects from the Swedish obese subjects cohort. Metabolism 2003; 52: 881–4.
- 46Tso AW, Sham PC, Wat NM, Xu A, Cheung BM, Rong R et al. Polymorphisms of the gene encoding adiponectin and glycaemic outcome of Chinese subjects with impaired glucose tolerance: a 5-year follow-up study. Diabetologia 2006; 49: 1806–15.
- 47Fumeron F, Aubert R, Siddiq A, Betoulle D, Pean F, Hadjadj S et al. Adiponectin gene polymorphisms and adiponectin levels are independently associated with the development of hyperglycemia during a 3-year period: the epidemiologic data on the insulin resistance syndrome prospective study. Diabetes 2004; 53: 1150–7.
- 48Zacharova J, Chiasson JL, Laakso M. The common polymorphisms (single nucleotide polymorphism [SNP] +45 and SNP +276) of the adiponectin gene predict the conversion from impaired glucose tolerance to type 2 diabetes: the STOP-NIDDM trial. Diabetes 2005; 54: 893–9.
- 49Menzaghi C, Ercolino T, Di Paola R, Berg AH, Warram JH, Scherer PE et al. A haplotype at the adiponectin locus is associated with obesity and other features of the insulin resistance syndrome. Diabetes 2002; 51: 2306–12.
- 50Yang WS, Tsou PL, Lee WJ, Tseng DL, Chen CL, Peng CC et al. Allele-specific differential expression of a common adiponectin gene polymorphism related to obesity. J Mol Med (Berl) 2003; 81: 428–34.
- 51Bowden DW, An SS, Palmer ND, Brown WM, Norris JM, Haffner SM et al. Molecular basis of a linkage peak: exome sequencing and family-based analysis identify a rare genetic variant in the ADIPOQ gene in the IRAS Family Study. Hum Mol Genet 2010; 19: 4112–20.
