Obesity and the role of genetic polymorphism: A review of genes as the risk of obesity

https://doi.org/10.19106/JMedSci005402202209

Pramudji Hastuti(1*)

(1) Department of Biochemistry, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
(*) Corresponding Author

Abstract


Obesity can be caused by environmental factors, which are higher energy input or lower energy expenditure. Environmental factors supported by genetic factors cause a person to have a different risk for developing obesity from to another. Genetics factors cause obesity through several pathways, which are impaired regulation in the hypothalamus and the regulation of energy expenditure. Obesity may be caused by one gene as monogenic-associated obesity, however, commonly caused by several genes together with environmental factors as the main multi-factorial risk of obesity. Obesity causes inflammation which leads to metabolic diseases. Many efforts are performed to prevent or treat obesity through the intervention to environmental and or genetic factors. Many attempts to reduce the prevalence of obesity were performed by influencing the environmental risk factors or the genetic risk factors. In this review, we identified the main genes which influence obesity. The genetic risks of obesity may be different from one to another country or between ethnic groups. Therefore, a better treatment approach should consider the differences role of genes in obesity rather than only changes in lifestyle. Nutrigenetic approach by considering the difference role of gens in responding to nutrients or drugs is recommended in individualized treatment plans.


Keywords


energy expenditure; genetic; nutrigenetic; obesity; polymorphism

Full Text:

PDF


References


1.Blüher M. Obesity: Global epidemiology and pathogenesis. Nat Rev Endocrinol 2019;15(5):288-98.
https://doi.org/10.1038/s41574-019-0176-8
2.Albuquerque D, Nóbrega C, Manco L, Padez C. The contribution of genetics and environment to obesity. Br Med Bull 2017;123(1):159-73.
https://doi.org/10.1093/bmb/ldx022
3.Rohde K, Keller M, la Cour Poulsen L, Blüher M, Kovacs P, Böttcher Y. Genetics and epigenetics in obesity. Metabolism 2019;92:37-50.
https://doi.org/10.1016/j.metabol.2018.10.007
4.Pinto RM, Steinmetz LS, Barbosa JMG, Mendes AFCS, Curado MP, da Cruz AD. The role of genetics in the pathophysiology of obesity: A systematic review. Obes Res - Open J 2019;6(1):11-7.
https://doi.org/10.17140/OROJ-6-137
5.Huvenne H, Dubern B, Clément K, Poitou C. Rare genetic forms of obesity: Clinical approach and current treatments in 2016. Obes Facts 2016;9(3):158-73.
https://doi.org/10.1159/000445061
6.Timper K, Brüning JC. Hypothalamic circuits regulating appetite and energy homeostasis: Pathways to obesity. DMM Dis Model Mech 2017;10(6):679-89.
https://doi.org/10.1242/dmm.026609
7.Singh RK, Kumar P, Mahalingam K. Molecular genetics of human obesity: A comprehensive review. Comptes Rendus - Biol 2017;340(2):87-108.
https://doi.org/10.1016/j.crvi.2016.11.007
8.Shabana and Hasnain S. Prevalence of POMC R236G mutation in Pakistan. Obes Res Clin Pract 2016; 10(1):S110-6.
9.Yang Y, Xu Y. The central melanocortin system and human obesity. J Mol Cell Biol 2021;12(10):785-97.
https://doi.org/10.1093/jmcb/mjaa048
10.Hastuti P, Tasmini, Cholid A, Sadewa AH. Polymorphism of prohormone convertase-1 and pro-opiomelanocortin associated with leptin level in Javanese ethnic of Indonesia. AIP Conf Proc 2019.
https://doi.org/10.1063/1.5098413
11.Yeung EH, Zhang C, Chen J, Bowers K, Hu FB, Kang G, Qi L. Polymorphisms in the neuropeptide Y gene and the risk of obesity: findings from two prospective cohorts. J Clin Endocrinol Metab 2011; 96(12):E2055-62.
https://doi.org/10.1210/jc.2011-0195
12.Ding B, Kull B, Liu Z, Mottagui-Tabar S, Thonberg H, Gu HF, et al. Human neuropeptide Y signal peptide gain-of-function polymorphism is associated with increased body mass index: possible mode of function. Regul Pept 2005; 127(1-3):45-53.
https://doi.org/10.1016/j.regpep.2004.10.011
13.Aberle J, Flitsch J, Beck NA, Mann O, Busch P, Peitsmeier P, et al. Genetic variation may influence obesity only under conditions of diet: analysis of three candidate genes Mol Genet Metab, 2008; 95:188-91.
https://doi.org/10.1016/j.ymgme.2008.07.008
14.Kulanuwat S, Santiprabhob J, Phonrat B, Limwongse C. Association between rs155971 in the PCSK1 gene and the lipid profile of obese Thai children: A family-based study. Genet Mol Res 2015; 14(3):9136-44.
https://doi.org/10.4238/2015.August.7.23
15.Chen Y, Snieder H, Wang X, Kaviya B, McCaffrey C, Spector TD, et al. Proopiomelanocortin gene variants are associated with serum leptin and body fat in normal female population. Eur J Hum Genet 2005;13(6): 772-80.
https://doi.org/10.1038/sj.ejhg.5201407
16.Yang F, Yang F, Tao YX. Biased signaling in naturally occurring mutations in human melanocortin-3 receptor gene. Int J Biol Sci 2015;11(4):423-33.
https://doi.org/10.7150/ijbs.11032
17.Stijnen P, Ramos-Molina B, O'Rahilly S, Creemers JWM. PCSK1 mutations and human endocrinopathies: From obesity to gastrointestinal disorders. Endocr Rev 2016;37(4):347-71.
https://doi.org/10.1210/er.2015-1117
18.Klein S, Romijn JA. Obesity. In: Melmed S, Polonsky KS, Larsen PR, Kronenberg HM editors, William Texbook of Endocrinology, 13th ed. Philadephia: Elsevier Inc., 2016.
https://doi.org/10.1016/B978-0-323-29738-7.00036-8
19.Courbage S, Poitou C, Le Beyec-Le Bihan J , Karsenty A, Lemale J, Pelloux V, et al. Implication of heterozygous variants in genes of the leptin-melanocortin pathway in severe obesity. J Clin Endocrinol Metab 2021; 106(10): 2991-3006.
https://doi.org/10.1210/clinem/dgab404.
20.Arianti R, Ariani NL, Muhammad A, Sadewa AH, Farmawati A, Sunarti, et al. Influence of single nucleotide polymorphism of ENPP1 and ADIPOQ on insulin resistance and obesity: A case-control study in a Javanese population. Life 2021;11: 552.
https://doi.org/10.3390/life11060552
21.Hsiao TJ, Lin E. The ENPP1 K121Q polymorphism is associated with type 2 diabetes and related metabolic phenotypes in a Taiwanese population. Mol Cell Endocrinol 2016; 433: 20-5.
22.Weedon MN, Shields B, Hitman G, Walker M, McCarthy MI, Hattersley AT, et al. No evidence of associa‐ tion of ENPP1 variants with type 2 diabetes or obesity in a study of 8089 U.K. Caucasians. Diabetes 2006; 55: 3175-9.
https://doi.org/10.2337/db06-0410
23.Morandi A, Pinelli L, Petrone A, Vatin V, Buzzetti R, Froguel P, et al. The Q121 variant of ENPP1 may protect from childhood overweight/obesity in the Italian population. Obesity 2006; 17: 202-6.
https://doi.org/10.1038/oby.2008.470
24.Baker M, Gaukrodger N, Mayosi BM, Imrie H, Farrall M, Watkins H, et al. Association between common polymorphisms of the proopiomelanocortin gene and body fat distribution: a family study. Diabetes 2005; 54(8): 2492-6.
https://doi.org/10.2337/diabetes.54.8.2492
25.Wang R, Zhou D, Xi B, Ge X, Zhu P, Wang B, et al. Association between vitamin D receptor gene polymorphisms and bone mineral density in Chinese women. Biomed Environ Sci 2012; 24(2): 200-6.
26.Bochenski J, Placha G, Wanic K, Malecki M, Sieradzki J, Warram JH, et al. New polymorphism of ENPP1 (PC-1) is associated with increased risk of type 2 diabetes among obese individuals. Diabetes. 2006;55(9): 2626-30.
https://doi.org/10.2337/db06-0191
27.Zorena K, Jachimowicz-Duda O, Ślęzak D, Robakowska M, Mrugacz M. Adipokines and obesity: Potential link to metabolic disorders and chronic complications. Int J Mol Sci. 2020;21(10): 18 pages.
https://doi.org/10.3390/ijms21103570
28.Hastuti P, Zukhrufia I, Padwaswari MH, Nuraini A, Sadewa AH. Polymorphism in leptin receptor gene was associated with obesity in Yogyakarta, Indonesia. Egypt J Med Hum Genet 2016;17(3):271-6.
https://doi.org/10.1016/j.ejmhg.2015.12.011
29.Hastuti P, Muhammad A. Correlation of leptin receptor gene variation with blood pressure and glucose level in type 2 diabetes mellitus subjects of Ternate population, East of Indonesia. Mal J Med Health Sci 2020; 16(SUPP3): 56-61.
30.Wu J, Zhuo Q, Chen X, Tian Y, Piao J, Yang X. Association of leptin receptor gene polymorphrism with metabolic syndrome in older Han adults from major cities in China. Wei Sheng Yan Jiu 2016;45(3): 376-82.
31.Lian Y, Tang Z, Xie Y, Chen Z. Leptin receptor gene polymorphisms and risk of hypertension: a meta- analysis. Int J Clin Exp Med 2015; 8(8):14277-82.
32.Gu P, Jiang W, Chen M, Lu B, Shao J, Du H, et al. Association of leptin receptor gene polymorphisms and essential hypertension in a Chinese population. J Endocrinol Invest 2012;35(9):859-65.
33.Komşu-Örnek Z, Demirel F, Dursun A, Ermiş B, Pişkin IE, Bideci A. Leptin receptor gene Gln223Arg polymorphism is not associated with obesity and metabolic syndrome in Turkish children. Turkish J Ped 2012;54(1): 20-4.
34.Pena GG, Guimarães ALS, Veloso RR, Reis TC, Gomes CS, Neto JFR, et al. Leptin receptor gene Gln223Arg polymorphism is not associated with hypertension: a preliminary population-based cross-sectional study. Cardiol Res Pract 2002; 879037: 7 pages.
35.Clément K, Mosbah H, Poitou C. Rare genetic forms of obesity: From gene to therapy: physiol Behav 2020; 227:113134.
https://doi.org/10.1016/j.physbeh.2020.113134
36.Schneider K, Valdez J, Nguyen J, Vawter M, Galke B, Kurtz TW, et al. Increased energy expenditure, Ucp1 expression, and resistance to diet-induced obesity in mice lacking nuclear factor-erythroid-2-related transcription factor-2 (Nrf2). J Biol Chem 2016; 291(14):7754-66.
https://doi.org/10.1074/jbc.M115.673756
37.Sreedhar A, Zhao Y. Uncoupling protein 2 and metabolic diseases. Mitochondrion 2017; 34:135-40.
https://doi.org/10.1016/j.mito.2017.03.005
38.Pravednikova AE, Shevchenko SY, Kerchev VV, Skhirtladze MR, Larina SN, Kachaev ZM, et al. Association of uncoupling protein (Ucp) gene polymorphisms with cardiometabolic diseases. Mol Med 2020;26(1):51.
https://doi.org/10.1186/s10020-020-00180-4
39.Surniyantoro HNE, Sadewa AH, Hastuti P. Uncoupling protein 2 (UCP2) as genetic risk factor for obesity in Indonesia is different in gender stratification. Kobe J Med Sci 2018; 64(2):E64-72.
40.Dalgaard LT, Andersen G, Larsen LH, Sørensen TI, Andersen T, Drivsholm T, et al. Mutational analysis of the UCP2 core promoter and relationships of variants with obesity. Obes Res 2003;11(11):1420-7.
https://doi.org/10.1038/oby.2003.191
41.Oktavianthi S, Trimarsanto H, Febinia CA, Suastika K, Saraswati MR, Dwipayana P, et al. Uncoupling protein 2 gene polymorphisms are associated with obesity. Cardiovasc Diabetol 2012;11:41.
https://doi.org/10.1186/1475-2840-11-41
42.Zhang M, Wang M, Zhao ZT. Uncoupling protein 2 gene polymorphisms in association with overweight and obesity susceptibility: a meta-analysis. Meta Gene 2014; 2:143-59.
https://doi.org/10.1016/j.mgene.2013.10.009
43.Lee YH, Kim W, Yu BC, Park BL, Kim LH, Shin HD. Association of the ins/del polymorphisms of uncoupling protein 2 (UCP2) with BMI in a Korean population. Biochem Biophys Res Commun 2008; 371(4):767-71.
https://doi.org/10.1016/j.bbrc.2008.04.144
44.Shiinoki T, Suehiro T, Ikeda Y, Inoue M, Nakamura T, Kumon Y, et al. Screening for variants of the uncoupling protein 2 gene in Japanese patients with non-insulin-dependent diabetes mellitus. Metabolism 1999; 48(5):581-4.
https://doi.org/10.1016/S0026-0495(99)90054-9
45.Xu K, Zhang M, Cui D, Fu Y, Qian L, Gu R, Wang M, Shen C, Yu R, Yang T. UCP2 -866G/A and Ala55Val, and UCP3 -55C/T polymorphisms in association with type 2 diabetes susceptibility: a meta-analysis study. Diabetologia 2011;54(9):2315-24.
https://doi.org/10.1007/s00125-011-2245-y
46.Avesani CM, Kamimura MA, Utaka S, Pecoits-Filho R, Nordfors L, Stenvinkel P, et al. Is UCP2 gene polymorphism associated with decreased resting energy expenditure in nondialyzed chronic kidney disease patients? J Ren Nutr 2008;18(6):489-94.
https://doi.org/10.1053/j.jrn.2008.08.009
47.Maestrini S, Podestà F, Di Blasio AM, Savia G, Brunani A, Tagliaferri A, et al. Lack of association between UCP2 gene polymorphisms and obesity phenotype in Italian Caucasians. J Endocrinol Invest. 2003; 26(10):985-90.
https://doi.org/10.1007/BF03348196
48.Otabe S, Clement K, Rich N, Warden C, Pecqueur C, Neverova M, et al. Mutation screening of the human UCP 2 gene in normoglycemic and NIDDM morbidly obese patients: lack of association between new UCP 2 polymorphisms and obesity in French Caucasians. Diabetes 1998; 47(5):840-2.
https://doi.org/10.2337/diabetes.47.5.840
49.Szendrei B, González-Lamuño D, Amigo T, Wang G, Pitsiladis Y, Benito PJ, et al. Influence of ADRB2 Gln27Glu and ADRB3 Trp64Arg polymorphisms on body weight and body composition changes after a controlled weight-loss intervention. Appl Physiol Nutr Metab 2015;41(3):307-14.
https://doi.org/10.1139/apnm-2015-0425
50.Leite N, Lazarotto L, Milano GE, Titski AC, Consentino CL, de Mattos F, et al. Associação do gene ADRB2 com sobrepeso e asma em crianças e adolescentes e sua relação com a aptidão física [Beta 2-adrenergic receptor gene association with overweight and asthma in children and adolescents and its relationship with physical fitness]. Rev Paul Pediatr 2015; 33(4):381-6.
https://doi.org/10.1016/j.rpped.2015.01.012
51.Shafriani NR, Hastuti P, Sadewa AH. Heterozygote polymorphisms of ARG16GLY and GLN27GLU ADRB2 gene is risk protective for obesity in Javanese population of Indonesia. African J Biotechnol 2018;17(37):1172-9.
https://doi.org/10.5897/AJB2018.16514
52.Gjesing AP, Andersen G, Burgdorf KS, Borch-Johnsen K, Jørgensen T, Hansen T, et al. Studies of the associations between functional beta2-adrenergic receptor variants and obesity, hypertension and type 2 diabetes in 7,808 white subjects. Diabetologia 2007;50(3):563-8.
https://doi.org/10.1007/s00125-006-0578-8
53.Kim SH, Kim DJ, Seo IA, Min YK, Lee MS, Kim KW, et al. Significance of beta2-adrenergic receptor gene polymorphism in obesity and type 2 diabetes mellitus in Korean subjects. Metabolism 2002;51(7):833-7.
https://doi.org/10.1053/meta.2002.33347
54.Kawamura T, Egusa G, Fujikawa R, Okubo M. Gln27Glu variant of the beta2-adrenergic receptor gene is not associated with obesity and diabetes in Japanese-Americans. Metabolism. 2001; 50(4):443-6.
https://doi.org/10.1053/meta.2001.21695
55.Castro AM, Macedo-de la Concha LE, Pantoja-Meléndez CA. Low-grade inflammation and its relation to obesity and chronic degenerative diseases. Rev Médica del Hosp Gen México. 2017;80(2):101-5.
https://doi.org/10.1016/j.hgmx.2016.06.011
56.Metz S, Huang LO, Kilpeläinen TO. Genetic variation, adipokines, and cardiometabolic disease. Curr Opin Pharmacol 2020; 52:33-9.
https://doi.org/10.1016/j.coph.2020.04.006
57.Recinella L, Orlando G, Ferrante C, Chiavaroli A, Brunetti L, Leone S. Adipokines: new potential therapeutic target for obesity and metabolic, rheumatic, and cardiovascular diseases. Front Physiol 2020;11:1-32.
https://doi.org/10.3389/fphys.2020.578966
58.Kasap T, Samet O, Omar A, Ali G. +45T>G single nucleotide polymorphism of adiponectin gene: Is it a factor in childhood obesity? J Clin Anal Med 2018; 9(5): 376-80.
http://doi.org/10.4328/jcam.5735
59.Mackawy AMH, Alzohairy MA, Ahmed EA, Badawy MEH. Adiponectin gene polymorphism and the incidence of type 2 diabetes mellitus in obese patients in Qassim Region, Saudi Arabia. J Am Sci 2011; 7: 432-43.
60.Khabour OF, Alomari MA, Abu Obaid AA. The Relationship of adiponectin level and ADIPOQ gene variants with BMI among young adult women. Dermatoendocrinol 2018; 10(1):e1477902.
https://doi.org/10.1080/19381980.2018.1477902
61.Gui MH, Li X, Jiang SF, Gao J, Lu DR, Gao X. Association of the adiponectin gene rs1501299 G>T variant, serum adiponectin levels, and the risk of coronary artery disease in a Chinese population. Diabetes Res Clin Pract 2012;97(3):499-504.
https://doi.org/10.1016/j.diabres.2012.05.011
62.Al-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(1):142-7.
https://doi.org/10.1016/j.gene.2011.11.045
63.Leu HB, Chung CM, Lin SJ, Jong YS, Pan WH, Chen JW. Adiponectin gene polymorphism is selectively associated with the concomitant presence of metabolic syndrome and essential hypertension. PLoS One 2011;6(5):e19999.
https://doi.org/10.1371/journal.pone.0019999
64.Dasari R, Raghunath V. Obesity and type II diabetes mellitus: Is resistin the link? J Diabetes Endocr Pract. 2018;1(1):1.
65.Acquarone E, Monacelli F, Borghi R, Nencioni A, Odetti P. Resistin: A reappraisal. Mech Ageing Dev 2019;178:46-63.
https://doi.org/10.1016/j.mad.2019.01.004
66.Pandey R. Resistin, is there any role in the mediation of obesity, insulin resistance and type-II diabetes mellitus? Juniper Online J Case Stud 2018;6(3):10-13.
https://doi.org/10.19080/JOJCS.2018.06.555686
67.Hastuti P, Tasmini T, Utami RF, Kaita Riwa MR, Steven S, Sadewa AH. Variation of resistin gene is correlated with insulin resistance in obese people of Indonesia. Open Access Maced J Med Sci 2019;7(12):1891-5.
https://doi.org/10.3889/oamjms.2019.456
68.Utami RF, Hastuti P, Sadewa AH. RETN rs3745368 polymorphism and resistin level in Javanese ethnic Indonesian obese: A case-control study. J Tekn Lab 2019; 8(1): 41- 9.
https://doi.org/10.29238/teknolabjournal.v8i1.164
69.Menzaghi C & Trischitta V. Genetics of serum resistin: A paradigm of population-specific regulation? Diabetologia. 2010; 53:226-8.
https://doi.org/10.1007/s00125-009-1589-z
70.Silswal N, Singh AK, Aruna B, Mukhopadhyay S, Ghosh S, Ehtesham NZ. Human resistin stimulates the pro-inflammatory cytokines TNF-alpha and IL-12 in macrophages by NF-kappaB-dependent pathway. Biochem Biophys Res Commun 2005;334(4):1092-101.
https://doi.org/10.1016/j.bbrc.2005.06.202
71.Menezes CA, de Oliveira Andrade LJ, Pinheiro JJ, Correia GS, de Melo PRS, et al. Tumor necrosis factor alpha -308 promoter polymorphism and insulin resistance in overweight and obese adolescents. Med 2017;50(6):358-64.
https://doi.org/10.11606/issn.2176-7262.v50i6p358-364
72.Mărginean CO, Mărginean C, Meliţ LE. New insights regarding genetic aspects of childhood obesity: A minireview. Front Pediatr 2018;6:1-8.
https://doi.org/10.3389/fped.2018.00271
73.Kern L, Mittenbühler MJ, Vesting AJ, Ostermann AL, Wunderlich CM, Wunderlich FT. Obesity-induced TNFα and IL-6 signaling: The missing link between obesity and inflammation- driven liver and colorectal cancers. Cancers (Basel) 2019;11(1):1-21.
https://doi.org/10.3390/cancers11010024
74.Hastuti P, Martantiningtyas DC, Karita D, Tasmini, Sadewa AH. Polymorphism of -308 G/A TNF- gene correlated with the concentration of TNF- and lipid profile in obese subject of Javanese population. African J Biotechnol 2017;16(37):1849-54.
https://doi.org/10.5897/AJB2017.16150
75.Pyrzak B, Wisniewska A, Popko K, Demkow U, Kucharska AM. Association between anthropometric measures of obesity, metabolic disturbances and polymorphism G-308A of the tumor necrosis factoralpha gene in children. Euro J Med Res 2010; 15(Suppl 2):141-6.
https://doi.org/10.1186/2047-783X-15-S2-141
76.Flores-Ramos LG, Escoto-De Dios A, Puebla-Pérez AM, FigueraVillanueva LE, Ramos- Silva A, Ramírez-Patiño R. Association of the tumor necrosis factor-alpha -308G>A polymorphism with breast cancer in Mexican women. Genet Mol Res 2013; 12(4):5680-93
https://doi.org/10.4238/2013.November.18.17
77.Li YY. Tumor necrosis factor-Alpha G308α gene polymorphism and essential hypertension: A Meta-analysis involving 2244 participants. PLoS One 2012; 7(4):e35408.
https://doi.org/10.1371/journal.pone.0035408
78.Bonyadi M, Abdolmohammadi R, Jahanafrooz Z, Somy MH, Khoshbaten M. TNF-alpha gene polymorphisms in Iranian Azari Turkish patients with inflammatory bowel diseases. Saudi J Gastroenterol 2014; 20:108-12.
https://doi.org/10.4103/1319-3767.129475
79.Hu M, Yu Z, Luo D, Zhang H, Li J, Liang F, et al. Association between -174G>C polymorphism in the IL-6 promoter region and the risk of obesity: A meta-analysis. Medicine (Baltimore). 2018; 97(33):e11773.
https://doi.org/10.1097/MD.0000000000011773
80.Hastuti P, Martantiningtyas DC, Karita D, Tasmini, Sadewa AH. Association of-174 g>c interleukin-6 gene polymorphism with interleukin-6 and c-reactive protein levels and obesity: A case-control study among people/residents of Western Indonesia. Med J Malaysia 2019;74(5):400-4.
81.Boeta-Lopez K, Duran J, Elizondo D, Gonzales E, Rentfro A, Schwarzbach AE, Nair S. Association of interleukin-6 polymorphisms with obesity or metabolic traits in young Mexican-Americans. Obes Sci Pract 2017;4(1):85-96.
https://doi.org/10.1002/osp4.138
82.Ramírez-López G, Portilla-de Buen E, Sánchez-Corona J, Salmerón-Castro J, Mendoza-Carrera F. Interleukin-6 polymorphisms are associated with obesity and hyperglycemia in Mexican adolescents. Arch Med Res 2013; 44(1):62-8.
https://doi.org/10.1016/j.arcmed.2012.10.019
83.Berthier M, Paradis A, Tchernof A, Bergeron J, Prud'homme D, Després J, et al. The interleukin 6 -174G/C polymorphism is associated with indices of obesity in men. J Hum Genet 2003; 48: 14-9.
https://doi.org/10.1007/s100380300002
84.Joffe YT, van der Merwe L, Evans J, Collins M, Lambert EV, September AV, et al. Interleukin-6 gene polymorphisms, dietary fat intake, obesity and serum lipid concentrations in black and white South African women. Nutrients 2014; 6: 2436-65.
https://doi.org/10.3390/nu6062436
85.Jenkins HN, Rivera-Gonzalez O, Gibert Y, Speed JS. Endothelin-1 in the pathophysiology of obesity and insulin resistance. Obes Rev 2020;21(12):1-9.
https://doi.org/10.1111/obr.13086
86.Karita D, Sadewa AH, Hastuti P. Association between polymorphism of lys 198 asn endothelin-1 gene and endothelin-1 plasma level in Javanese obesity population. Bangladesh J Med Sci 2019;18(1):46-9.
https://doi.org/10.3329/bjms.v18i1.39546
87.Ahmed M, Rghigh A. Polymorphism in endothelin-1 gene: An overview. Curr Clin Pharmacol 2016;11(3):191-210.
https://doi.org/10.2174/1574884711666160701000900



DOI: https://doi.org/10.19106/JMedSci005402202209

Article Metrics

Abstract views : 2952 | views : 3214




Copyright (c) 2022 Pramudji Hastuti

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

View My Stats

 

Creative Commons License
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) by  Universitas Gadjah Mada is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.