Screening rs2241766 Polymorphism as a Susceptibility Index Parameter in Obese Patients with a High Level of Cholesterol

Document Type : Research Article

Authors

1 Department of Cell and Molecular Biology, Faculty of Chemistry, University of Kashan, Kashan, Isfahan, Iran

2 Department of Genetics, Faculty of Science, Shahrekord University, Shahrekord, Iran

Abstract

Obesity is a multifactorial disorder that has increased dramatically in recent years in developing countries. The disproportion of energy uptake and expenditure, which is the result of several factors such as diet, behavior, environment, as well as metabolic and genetic factors, could eventually lead to this disease. Mutations in genes that regulate appetite and metabolism could affect various aspects of obesity. Adiponectin protein, the product of the ADIPOQ gene, is an essential adipokine for controlling energy homeostasis and fat storage and is secreted in white adipose tissues. It is an insulin-sensitive hormone whose blood concentration declines in obesity. In this study, we examined the association of rs2241766 +45 T>G polymorphism of the ADIPOQ gene with obesity and blood levels of High-Density Lipoprotein (HDL), Low-Density Lipoprotein (LDL), Triglyceride (TG), and total cholesterol in the population of Borujen City. In this case-control study, blood samples were collected from people referred to Tamin Ejtemaee Laboratory of Borujen who suffered from obesity problems. Triglyceride, total cholesterol, LDL, and HDL levels were analyzed in the patient's blood using the alpha6 auto-analyzer. In the next step, total DNA was extracted from the blood samples and subjected to Restriction Fragment Length Polymorphism (RFLP) methods to investigate the rs2241766 polymorphism of the ADIPOQ gene. According to the results of this study, there is no significant correlation between any alleles and genotypes of this polymorphism with obesity (Chi-square p-value was 0.82 and 0.85 respectively for alleles and genotypes, odds-ratio 1.155, 95% CI= 0.32-4.14). There is no significant correlation between the blood lipid characteristics of the patients and the genotypes of the studied polymorphism. According to our results, it seems that the alleles and genotypes of the ADIPOQ gene rs2241766 do not affect the etiology of obesity in our samples.

Keywords

References

Al-Daghri NM, Al-Attas OS, Alokail MS, Alkharfy KM, Hussain T, Yakout S, …, Sabico S. 2012. Adiponectin gene polymorphisms (T45G and G276T), adiponectin levels and risk for metabolic diseases in an Arab population. Gene 493(1): 142-147.
AlSaleh A, Sanders TA, O'Dell SD. 2012. Effect of interaction between PPARG, PPARA and ADIPOQ gene variants and dietary fatty acids on plasma lipid profile and adiponectin concentration in a large intervention study. Proc Nutr Soc 71(1): 141-153.
Ambroziak M, Kolanowska M, Bartoszewicz Z, Budaj A. 2018. Adiponectin gene variants and decreased adiponectin plasma levels are associated with the risk of myocardial infarction in young age. Gene 642: 498-504.
Barliana MI, Yolanda PD, Rostinawati T, Ng H, Alfian SD, Abdulah R, Diantini A. 2019. Polymorphism of the APM1 gene in subjects with central obesity related to lower high-density lipoprotein cholesterol. Diabetes Metab Syndr Obes 12: 2317-2324.
Bermúdez-Cardona J, Velásquez-Rodríguez C. 2016. Profile of free fatty acids and fractions of phospholipids, cholesterol esters and triglycerides in serum of obese youth with and without metabolic syndrome. Nutrients 8(2): 54. doi:10.3390/nu8020054
Bogers RP, Bemelmans WJ, Hoogenveen RT, Boshuizen HC, Woodward M, Knekt P, …, BMI-CHD collaboration investigators. 2007. Association of overweight with increased risk of coronary heart disease partly independent of blood pressure and cholesterol levels: a meta-analysis of 21 cohort studies including more than 300 000 persons. Arch Intern Med 167(16): 1720-1728.
Bouchard C. 2008. Gene environment interactions in the etiology of obesity: defining the fundamentals. Obesity (Silver Spring) Suppl 3:S5-S10.
Breitfeld J, Stumvoll M, Kovacs P. 2012. Genetics of adiponectin. Biochimie 94(10): 2157-2163.
Butler JM. 2011. Advanced topics in forensic DNA typing: methodology. Academic press, Massachusetts, USA.
de Luis DA, Calvo SG, Pacheco D, Ovalle HF, Aller R. 2018. Adiponectin gene variant RS rs266729: relation to lipid profile changes and circulating adiponectin after bariatric surgery. Surg Obes Relat Dis 14(9): 1402-1408.
Di Pietro F, Ortenzi F, Tilio M, Concetti F, Napolioni V. 2011. Genomic DNA extraction from whole blood stored from 15-to 30-years at -20 C by rapid phenol–chloroform protocol: A useful tool for genetic epidemiology studies. Mol Cell Probes 25(1): 44-48.
Divella R, Daniele A, Mazzocca A, Abbate I, Casamassima P, Caliandro C, ..., De Luca R. 2017. ADIPOQ rs266729 G/C gene polymorphism and plasmatic adipocytokines connect metabolic syndrome to colorectal cancer. J Cancer 8(6): 1000- 1008.
Elghazy AM, Elsaeid AM, Refaat M, Youssef MM. 2019. Biochemical studies of adiponectin gene polymorphism in patients with obesity in Egyptians. Arch Physiol Biochem 128(1): 43-50.
Enns JE, Taylor CG, Zahradka P. 2011. Variations in adipokine genes AdipoQ, Lep, and LepR are associated with risk for obesity-related metabolic disease: the modulatory role of gene-nutrient interactions. J Obes 2011:168659.
Ergören MC, Söyler G, Sah H, Becer E. 2019. Investigation of potential genomic biomarkers for obesity and personalized medicine. Int J Biol Macromol 122: 493-498.
Feingold KR, Grunfeld C. 2018. Obesity and dyslipidemia. Metabolism 92:71-81
Greenberg AS, Obin MS. 2006. Obesity and the role of adipose tissue in inflammation and metabolism. Am J Clin Nutr 83(2): 461S-465S.
Gu HF. 2009. Biomarkers of adiponectin: plasma protein variation and genomic DNA polymorphisms. Biomarker Insights 4:123-133.
Guzman-Ornelas MO, Chavarria-Avila E, Munoz-Valle JF, Armas-Ramos LE, Castro-Albarran J, Aldrete MEA, …, Navarro-Hernandez RE. 2012. Association of ADIPOQ +45T>G polymorphism with body fat mass and blood levels of soluble adiponectin and inflammation markers in a Mexican-Mestizo population. Diabetes Metab Syndr Obes 5: 369-378.
Han Q, Geng W, Zhang D, Cai G, Zhu H. 2020. ADIPOQ rs2241766 gene polymorphism and predisposition to diabetic kidney disease. J Diabetes Res 2020: 5158497.
Ji ZY, Li HF, Lei Y, Rao YW, Tan ZX, Liu HJ, …, Sun ML. 2015. Association of adiponectin gene polymorphisms with an elevated risk of diabetic peripheral neuropathy in type 2 diabetes patients. J Diabetes Complicat 29(7): 887-892.
Johansson LE, Danielsson P, Norgren S, Marcus C, Ridderstråle M. 2009. Interaction between PPARG Pro12Ala and ADIPOQ G276T concerning cholesterol levels in childhood obesity. Int J Pediatr Obes 4(2): 119-125.
Kadouh HC, Acosta A. 2017. Current paradigms in the etiology of obesity. Tech Gastrointest Endosc 19: 2-11.
Kaftan AN, Hussain MK. 2015. Association of adiponectin gene polymorphism rs266729 with type two diabetes mellitus in Iraqi population. A pilot study. Gene 570(1): 95-99.
Karmelić I, Lovrić J, Božina T, Ljubić H, Vogrinc Ž, Božina N, Sertić J. 2012. Adiponectin level and gene variability are obesity and metabolic syndrome markers in a young population. Arch Med Res 43(2): 145-153.
Klop B, Elte JWF, Cabezas MC. 2013. Dyslipidemia in obesity: mechanisms and potential targets. Nutrients 5(4): 1218-1240.
Landecho MF, Tuero C, Valentí V, Bilbao I, de la Higuera M, Frühbeck G. 2019. Relevance of Leptin and Other Adipokines in obesity-associated cardiovascular risk. Nutrients 11(11): 2664.
Lim S, Quon MJ, Koh KK. 2014. Modulation of adiponectin as a potential therapeutic strategy. Atherosclerosis 233(2): 721-728.
Lindsay RS, Funahashi T, Krakoff J, Matsuzawa Y, Tanaka S, Kobes S, …, Hanson RL. 2003. Genome-wide linkage analysis of serum adiponectin in the Pima Indian population. Diabetes, 52(9): 2419-2425.
Melistas, L., Mantzoros, C. S., Kontogianni, M., Antonopoulou, S., Ordovas, J. M., & Yiannakouris, N. 2009. Association of the +45T>G and +276G>T polymorphisms in the adiponectin gene with insulin resistance in nondiabetic Greek women. Eur J Endocrinol 161(6): 845-852.
Muiya N, Al-Najai M, Tahir AI, Elhawari S, Gueco D, Andres E, …, Dzimiri N. 2013. The 3'-UTR of the adiponectin Q gene harbours susceptibility loci for atherosclerosis and its metabolic risk traits. BMC Med Genet 14: 127.
Park JW, Park J, Jee SH. 2011. ADIPOQ gene variants associated with susceptibility to obesity and low serum adiponectin levels in healthy Koreans. Epidemiol health 33:e2011003. doi: 10.4178/epih/e2011003
Payab M, Amoli MM, Qorbani M, Hasani-Ranjbar S. 2017. Adiponectin gene variants and abdominal obesity in an Iranian population. Eating and Weight Disorders-Studies on Anorexia, Bulimia and Obesity, 22(1): 85-90.
Persson J, Lindberg K, Gustafsson T, Eriksson P, Paulsson‐Berne G, Lundman P. 2010. Low plasma adiponectin concentration is associated with myocardial infarction in young individuals. J Intern Med 268(2): 194-205.
Petrone A, Zavarella S, Caiazzo A, Leto G, Spoletini M, Potenziani S, Osborn J, Vania A, Buzzetti R. 2006. The promoter region of the adiponectin gene is a determinant in modulating insulin sensitivity in childhood obesity. Obesity 14(9): 1498-1504.
Potapov VA, Chistiakov DA, Dubinina A, Shamkhalova MS, Shestakova MV, Nosikov VV. 2008. Adiponectin and adiponectin receptor gene variants in relation to type 2 diabetes and insulin resistance-related phenotypes. Rev Diabet Stud 5(1): 28- 37.
Rabiee F, Lachinani L, Ghaedi S, Nasr-Esfahani MH, Megraw TL, Ghaedi K. 2020. New insights into the cellular activities of Fndc5/Irisin and its signaling pathways. Cell Biosci 10(1): 1-10.
Ramya K, Ayyappa KA, Ghosh S, Mohan V, Radha V. 2013. Genetic association of ADIPOQ gene variants with type 2 diabetes, obesity and serum adiponectin levels in south Indian population. Gene 532(2): 253-262.
Satoh N, Wada H, Ono K, Yamakage H, Yamada K, Nakano T, …, Hasegawa K. 2008. Small dense LDL-cholesterol relative to LDL-cholesterol is a strong independent determinant of hypoadiponectinemia in metabolic syndrome. Circ J 72(6): 932-939.
Siitonen N, Pulkkinen L, Lindström J, Kolehmainen M, Eriksson JG, Venojärvi M, …, Uusitupa M. 2011. Association of ADIPOQ gene variants with body weight, type 2 diabetes and serum adiponectin concentrations: the Finnish Diabetes Prevention Study. BMC Med Genet 12(1): 1-13.
Subramanian S, Chait A. 2012. Hypertriglyceridemia secondary to obesity and diabetes. Biochim Biophys Acta 1821(5): 819-825.
Tu Y, Yu Q, Fan G, Yang P, Lai Q, Yang F, …, Wang CY. 2014. 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 396(1-2):1-9.
Vasseur F, Meyre D, Froguel P. 2006. Adiponectin, type 2 diabetes and the metabolic syndrome: lessons from human genetic studies. Expert Rev Mol Med 8(27): 1-12.
Wanders D, Plaisance EP, Judd RL. 2012. Lipid-lowering drugs and circulating adiponectin. Vitam Horm 90:341-374.
Wang H, Peng DQ. 2011. New insights into the mechanism of low high-density lipoprotein cholesterol in obesity. Lipids Health Dis 10(1): 1-10.
Warodomwichit D, Shen J, Arnett DK, Tsai MY, Kabagambe EK, Peacock JM, …, Ordovas JM. 2009. The monounsaturated fatty acid intake modulates the effect of ADIPOQ polymorphisms on obesity. Obesity (Silver Spring) 17(3): 510- 517.
Weinsier RL, Hunter GR, Heini AF, Goran MI, Sell SM. 1998. The etiology of obesity: relative contribution of metabolic factors, diet, and physical activity. Am J Med 105(2): 145-150.
Wu J, Liu Z, Meng K, Zhang L. 2014. Association of adiponectin gene (ADIPOQ) rs2241766 polymorphism with obesity in adults: a meta-analysis. PLoS One 9(4):e95270.
Yu Z, Han S, Cao X, Zhu C, Wang X, Guo X. 2012. Genetic polymorphisms in adipokine genes and the risk of obesity: a systematic review and meta‐analysis. Obesity (Silver Spring) 20(2): 396-406
Zhao N, Li N, Zhang S, Ma Q, Ma C, Yang X, …, Cui T. 2017. Associations between two common single nucleotide polymorphisms (rs2241766 and rs1501299) of ADIPOQ gene and coronary artery disease in type 2 diabetic patients: a systematic review and meta-analysis. Oncotarget 8(31):51994-52005.
Journal of Genetic Resources
Volume 8, Issue 2
2022
Pages 198-206

Files

Share

How to cite

Statistics