Association of ADIPOQ (rs2241767) and METRNL (rs147617313) gene polymorphisms with type 2 diabetes mellitus in the Vietnamese population: A case – control study
Main Article Content
Abstract
Adipokines derived from adipose tissue have been proven to participate in many metabolic pathways in the body. Adipokine dysregulation has been considered an important cause of many metabolic diseases, such as Type 2 Diabetes Mellitus (T2DM). Our research investigated the association between the two single-nucleotide polymorphisms of the ADIPOQ and METRNL genes with T2DM. A case-control study was conducted with 260 T2DM patients and 260 healthy controls. The ADIPOQ variant (rs2241767) and the METRNL variant (rs147617313) were determined based on polymerase chain reaction-restriction fragment length polymorphism. The rs147617313 locus of the METRNL gene showed only one homozygous genotype, CC. In the rs2241767 locus of the ADIPOQ gene, the genotype frequencies in the case group (AA: 41%, AG: 50%, GG: 9%) were similar to those in the control group (AA: 47%, AG: 40 %, GG: 13%). The AG genotype was associated with an increased risk of T2DM in the additive model (OR = 1.4; 95%CI: 1.0 – 2.09; p = 0.046). Of the two single-nucleotide polymorphisms, rs2241767 and rs147617313, only rs2241767 was associated with the risk of type 2 Diabetes Mellitus in Vietnamese people.
Article Details
Keywords
Adiponectin, variant, Subfatin, metabolic syndrome
References
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24. Bahia W, Soltani I, Haddad A, et al. Contribution of ADIPOQ Variants to the Genetic Susceptibility of Recurrent Pregnancy Loss. Reproductive sciences (Thousand Oaks, Calif). 2021;28(1):263-270.10.1007/s43032-020-00274-8
25. Otsuka H, Yanai M, Kobayashi H, et al. High-molecular-weight adiponectin levels in healthy, community-dwelling, elderly Japanese volunteers: a 5-year prospective observational study. Aging clinical and experimental research. 2018;30(7):791-798.10.1007/s40520-017-0840-6
26. Wang W-L, Zhu H, Xie Y, et al. Relation between ADIPOQ gene polymorphisms and type 2 diabetes in a Chinese population. International journal of clinical and experimental medicine. 2015;8(4):6124-6128.
27. Du W, Li Q, Lu Y, et al. Genetic variants in ADIPOQ gene and the risk of type 2 diabetes: a case–control study of Chinese Han population. Endocrine. 2011;40(3):413-422.10.1007/s12020-011-9488-8
28. Cui M, Gao Y, Zhao Y, et al. Association between Adiponectin Gene Polymorphism and Environmental Risk Factors of Type 2 Diabetes Mellitus among the Chinese Population in Hohhot. BioMed Research International. 2020;2020(6383906.10.1155/2020/6383906
29. Mtiraoui N, Ezzidi I, Turki A, et al. Single-nucleotide polymorphisms and haplotypes in the adiponectin gene contribute to the genetic risk for type 2 diabetes in Tunisian Arabs. Diabetes Res Clin Pract. 2012;97(2):290-297.https://doi.org/10.1016/j.diabres.2012.02.015
30. Zusi C, Csermely A, Rinaldi E, et al. Crosstalk between genetic variability of adiponectin and leptin, glucose-insulin system and subclinical atherosclerosis in patients with newly diagnosed type 2 diabetes. The Verona Newly Diagnosed Type 2 Diabetes Study 14. Diabetes, obesity & metabolism. 2023;25(9):2650-2658.10.1111/dom.15152
31. Cui M, Zhou S, Li R, et al. Association of ADIPOQ single nucleotide polymorphisms with the risk of intracranial atherosclerosis. The International journal of neuroscience. 2017;127(5):427-432.10.1080/00207454.2016.1190716
32. Wassel CL, Pankow JS, Rasmussen-Torvik LJ, et al. Associations of SNPs in ADIPOQ and subclinical cardiovascular disease in the multi-ethnic study of atherosclerosis (MESA). Obesity (Silver Spring). 2011;19(4):840-847.10.1038/oby.2010.229
33. Li H-J, Li C-P, Zhang C, et al. Association of Adiponectin gene polymorphisms and nonalcoholic fatty liver disease. Int J Biomed Clin Anal. 2015;8(9):16676-16681.
34. Chung H-F, Long KZ, Hsu C-C, et al. Adiponectin gene (ADIPOQ) polymorphisms correlate with the progression of nephropathy in Taiwanese male patients with type 2 diabetes. Diabetes Research and Clinical Practice. 2014;105(2):261-270.10.1016/j.diabres.2014.04.015
35. Park J, Kim I, Jung KJ, et al. Gene-gene interaction analysis identifies a new genetic risk factor for colorectal cancer. Journal of biomedical science. 2015;22(73.10.1186/s12929-015-0180-9
36. Singh O, Verma M, Dahiya N, et al. Integrating Polygenic Risk Scores (PRS) for Personalized Diabetes Care: Advancing Clinical Practice with Tailored Pharmacological Approaches. Diabetes Ther. 2025;16(2):149-168.10.1007/s13300-024-01676-6
2. Smith K, Deutsch AJ, McGrail C, et al. Multi-ancestry polygenic mechanisms of type 2 diabetes. Nat Med. 2024;30(4):1065-1074.10.1038/s41591-024-02865-3
3. Brunetti A, Chiefari E, Foti D. Recent advances in the molecular genetics of type 2 diabetes mellitus. World J Diabetes. 2014;5(2):128-140.10.4239/wjd.v5.i2.128
4. Deutsch AJ, Ahlqvist E, Udler MS. Phenotypic and genetic classification of diabetes. Diabetologia. 2022;65(11):1758-1769.10.1007/s00125-022-05769-4
5. Dornbos P, Koesterer R, Ruttenburg A, et al. A combined polygenic score of 21,293 rare and 22 common variants significantly improves diabetes diagnosis based on hemoglobin A1C levels. medRxiv. 2021;2021.2011.2004.21265868.10.1101/2021.11.04.21265868
6. Galic S, Oakhill JS, Steinberg GR. Adipose tissue as an endocrine organ. Mol Cell Endocrinol. 2010; 316(2): 129-139.https://doi.org/10.1016/j.mce.2009.08.018
7. Galic S, Oakhill JS, Steinberg GR. Adipose tissue as an endocrine organ. Mol Cell Endocrinol. 2010;316(2):129-139.10.1016/j.mce.2009.08.018
8. Recinella L, Orlando G, Ferrante C, et al. Adipokines: New Potential Therapeutic Target for Obesity and Metabolic, Rheumatic, and Cardiovascular Diseases. Front Physiol. 2020;11(578966.10.3389/fphys.2020.578966
9. Hotta K, Funahashi T, Arita Y, et al. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol. 2000;20(6):1595-1599.10.1161/01.atv.20.6.1595
10. Javor J, Ďurmanová V, Klučková K, et al. Adiponectin Gene Polymorphisms: A Case-Control Study on Their Role in Late-Onset Alzheimer’s Disease Risk. Life. 2024;14(3):346.10.3390/life14030346
11. Alimi M, Goodarzi MT, Nekoei M. Adiponectin gene polymorphisms and risk of type 2 diabetes: an updated evidence for meta-analysis. Diabetol Metab Syndr. 2021;13(1):133.10.1186/s13098-021-00749-x
12. Rao RR, Long JZ, White JP, et al. Meteorin-like is a hormone that regulates immune-adipose interactions to increase beige fat thermogenesis. Cell. 2014;157(6):1279-1291.10.1016/j.cell.2014.03.065
13. Shankar SS, Banarjee R, Jathar SM, et al. De novo structure prediction of meteorin and meteorin-like protein for identification of domains, functional receptor binding regions, and their high-risk missense variants. J Biomol Struct Dyn. 2024;42(9):4522-4536.10.1080/07391102.2023.2220804
14. Bello-Chavolla OY, Almeda-Valdes P, Gomez-Velasco D, et al. METS-IR, a novel score to evaluate insulin sensitivity, is predictive of visceral adiposity and incident type 2 diabetes. Eur J Endocrinol. 2018;178(5):533-544.10.1530/eje-17-0883
15. Truong S, Tran NQ, Ma PT, et al. Association of ADIPOQ Single-Nucleotide Polymorphisms with the Two Clinical Phenotypes Type 2 Diabetes Mellitus and Metabolic Syndrome in a Kinh Vietnamese Population. Diabetes Metab Syndr Obes. 2022;15(307-319.10.2147/dmso.s347830
16. dbSNP. rs147617313 [Homo sapiens]. https://www.ncbi.nlm.nih.gov/snp/?term=rs147617313. Updated
17. Le VS, Tran KT, Bui HTP, et al. A Vietnamese human genetic variation database. Hum Mutat. 2019;40(10):1664-1675.10.1002/humu.23835
18. Song Y, Choi JE, Kwon YJ, et al. Identification of susceptibility loci for cardiovascular disease in adults with hypertension, diabetes, and dyslipidemia. J Transl Med. 2021;19(1):85.10.1186/s12967-021-02751-3
19. Murai Y, Matano F, Kubota A, et al. RNF213-Related Vasculopathy: Various Systemic Vascular Diseases Involving RNF213 Gene Mutations: Review. J Nippon Med Sch. 2024;91(2):140-145.10.1272/jnms.JNMS.2024_91-215
20. Iyer KR, Clarke SL, Guarischi-Sousa R, et al. Unveiling the Genetic Landscape of Coronary Artery Disease Through Common and Rare Structural Variants. J Am Heart Assoc. 2025;14(4):e036499.10.1161/jaha.124.036499
21. Rajkumar AP, Christensen JH, Mattheisen M, et al. Analysis of t(9;17)(q33.2;q25.3) chromosomal breakpoint regions and genetic association reveals novel candidate genes for bipolar disorder. Bipolar Disord. 2015;17(2):205-211.10.1111/bdi.12239
22. Bermudo R, Abia D, Ferrer B, et al. Co-regulation analysis of closely linked genes identifies a highly recurrent gain on chromosome 17q25.3 in prostate cancer. BMC Cancer. 2008;8(315.10.1186/1471-2407-8-315
23. Liu M, Sariya S, Khasiyev F, et al. Genetic determinants of intracranial large artery stenosis in the northern Manhattan study. Journal of the neurological sciences. 2022;436(120218.10.1016/j.jns.2022.120218
24. Bahia W, Soltani I, Haddad A, et al. Contribution of ADIPOQ Variants to the Genetic Susceptibility of Recurrent Pregnancy Loss. Reproductive sciences (Thousand Oaks, Calif). 2021;28(1):263-270.10.1007/s43032-020-00274-8
25. Otsuka H, Yanai M, Kobayashi H, et al. High-molecular-weight adiponectin levels in healthy, community-dwelling, elderly Japanese volunteers: a 5-year prospective observational study. Aging clinical and experimental research. 2018;30(7):791-798.10.1007/s40520-017-0840-6
26. Wang W-L, Zhu H, Xie Y, et al. Relation between ADIPOQ gene polymorphisms and type 2 diabetes in a Chinese population. International journal of clinical and experimental medicine. 2015;8(4):6124-6128.
27. Du W, Li Q, Lu Y, et al. Genetic variants in ADIPOQ gene and the risk of type 2 diabetes: a case–control study of Chinese Han population. Endocrine. 2011;40(3):413-422.10.1007/s12020-011-9488-8
28. Cui M, Gao Y, Zhao Y, et al. Association between Adiponectin Gene Polymorphism and Environmental Risk Factors of Type 2 Diabetes Mellitus among the Chinese Population in Hohhot. BioMed Research International. 2020;2020(6383906.10.1155/2020/6383906
29. Mtiraoui N, Ezzidi I, Turki A, et al. Single-nucleotide polymorphisms and haplotypes in the adiponectin gene contribute to the genetic risk for type 2 diabetes in Tunisian Arabs. Diabetes Res Clin Pract. 2012;97(2):290-297.https://doi.org/10.1016/j.diabres.2012.02.015
30. Zusi C, Csermely A, Rinaldi E, et al. Crosstalk between genetic variability of adiponectin and leptin, glucose-insulin system and subclinical atherosclerosis in patients with newly diagnosed type 2 diabetes. The Verona Newly Diagnosed Type 2 Diabetes Study 14. Diabetes, obesity & metabolism. 2023;25(9):2650-2658.10.1111/dom.15152
31. Cui M, Zhou S, Li R, et al. Association of ADIPOQ single nucleotide polymorphisms with the risk of intracranial atherosclerosis. The International journal of neuroscience. 2017;127(5):427-432.10.1080/00207454.2016.1190716
32. Wassel CL, Pankow JS, Rasmussen-Torvik LJ, et al. Associations of SNPs in ADIPOQ and subclinical cardiovascular disease in the multi-ethnic study of atherosclerosis (MESA). Obesity (Silver Spring). 2011;19(4):840-847.10.1038/oby.2010.229
33. Li H-J, Li C-P, Zhang C, et al. Association of Adiponectin gene polymorphisms and nonalcoholic fatty liver disease. Int J Biomed Clin Anal. 2015;8(9):16676-16681.
34. Chung H-F, Long KZ, Hsu C-C, et al. Adiponectin gene (ADIPOQ) polymorphisms correlate with the progression of nephropathy in Taiwanese male patients with type 2 diabetes. Diabetes Research and Clinical Practice. 2014;105(2):261-270.10.1016/j.diabres.2014.04.015
35. Park J, Kim I, Jung KJ, et al. Gene-gene interaction analysis identifies a new genetic risk factor for colorectal cancer. Journal of biomedical science. 2015;22(73.10.1186/s12929-015-0180-9
36. Singh O, Verma M, Dahiya N, et al. Integrating Polygenic Risk Scores (PRS) for Personalized Diabetes Care: Advancing Clinical Practice with Tailored Pharmacological Approaches. Diabetes Ther. 2025;16(2):149-168.10.1007/s13300-024-01676-6