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Potential association of GCK rs2268576 and rs741038 polymorphisms with type 2 diabetes mellitus in the Turkish population

Year 2025, Volume: 38 Issue: 3, 242 - 251, 10.10.2025
https://doi.org/10.5472/marumj.1800187

Abstract

Objective: Polymorphisms, defined as variations in specific genes, are common in human populations and usually do not cause
disease. However, some may influence disease susceptibility or progression. This study aimed to investigate the potential association
of two glucokinase (GCK) gene polymorphisms (rs2268576 and rs741038) with the development and metabolic regulation of type 2
diabetes mellitus.
Patients and Methods: A total of 134 individuals were enrolled, including 58 patients with type 2 diabetes and 76 non-diabetic controls
from outpatient clinics. Genomic DNA was extracted from peripheral blood samples, and genotyping for rs2268576 and rs741038 was
performed using real-time polymerase chain reaction (PCR). Genotypic distributions were compared between groups and correlated
with laboratory parameters obtained during clinical follow-up.
Results: No significant differences were found in the genotypic distributions of rs2268576 and rs741038 between diabetic patients and
controls (P> 0.05). Similarly, no association was observed with fasting glucose, postprandial glucose, or HbA1c. However, individuals
with the GG genotype of rs741038 had significantly higher microalbumin/creatinine ratios (P = 0.03), suggesting a potential genetic
link to diabetic nephropathy despite no association with diabetes development.
Conclusion: Although, no relationship was found between these GCK polymorphisms and diabetes itself, the rs741038 GG genotype
may indicate risk for diabetic nephropathy, independent of glycemic control.

References

  • IDF Diabetes Atlas 2021, 10th edition https://diabetesatlas. org/atlas/tenth-edition/ (Accessed on January 17, 2022)
  • Ong KL, Stafford LK, McLaughlin SA, et al. (GBD 2021 Diabetes Collaborators) Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet 2023;402:203-34. doi:10.1016/S0140- 6736(23)01301-6.
  • American Diabetes Association. Standards of medical care in diabetes—2007. Diabetes Care 2007;30 Suppl 1: S4-S41. doi: 10.2337/dc07-S004. PMID: 17192377.
  • Henzen C. Monogenic diabetes mellitus due to defects in insulin secretion. Swiss Med Wkly 2012;142: w13690. doi: 10.4414/smw.2012.13690. PMID: 23037711.
  • Mughal SA, Thanabalasingham G, Owen KR. Biomarkers currently used for the diagnosis of maturity-onset diabetes of the young. Diabetes Management 2013;3: 71.doi:10.2217/dmt.12.82
  • Firdous P, Nissar K, Ali S, et al. Genetic testing of maturityonset diabetes of the young current status and future perspectives. Front Endocrinol (Lausanne) 2018; 9:253. doi:10.3389/fendo.2018.00253
  • Ansari N, Ramachandran V, Mohamad NA, et al. Associations of GCK (rs1799884), GCKR (rs780094), and G6PC2 (rs560887) gene polymorphisms with type 2 diabetes among Malay ethnics. Glob Med Genet 2023 ;10:12- 8. doi:10.1055/s-0042.176.0384
  • Li C, Yang Y, Liu X, Li Z, Liu H, Tan Q. Glucose metabolismrelated gene polymorphisms as the risk predictors of type 2 diabetes. Diabetol Metab Syndr 2020 ;12:97. doi: 10.1186/ s13098.020.00604-5.
  • Zhang X, Sun G, LI J, Han H, Chen, Q. Relationship between glucokinase gene 6 tag single nucleotide polymorphism sites and type 2 diabetes mellitus. Chin J Lab Med 2015;12: 827-32.
  • Yilmaz GS, Haliloglu B The role of glucokinase gen (GCK, MODY 2) variations in diabetes Panel-Abstracts.OP- 04 MEDICAL BIOCHEMISTRY 2018 ;1: 61.
  • Sun G, Zhang X, Li J, Han H, Chen Q. The relationship between glucokinase gene 4 tag single nucleotide polymorphism sites and type 2 diabetes mellitus Int J Lab Med 2016.; 12: 2507-10.
  • Bonnycastle LL, Willer CJ, Conneely KN, et al. Common variants in maturity-onset diabetes of the young genes contribute to risk of type 2 diabetes in Finns. Diabetes 2006;55:2534-40. doi: 10.2337/db06-0178
  • Frigeri HR, Auwerter NC, Koczicki L, et al. Polymorphisms rs144723656, rs2268574, and rs2268575 of the glucokinase gene are not associated with obese women with type 2 diabetes mellitus. Clin Biochem 2016 ;49:194-5. doi: 10.1016/j. clinbiochem. 2015.09.016.
  • Holmkvist J, Almgren P, Lyssenko V, et al. Common variants in maturity-onset diabetes of the young genes and future risk of type 2 diabetes. Diabetes 2008;57:1738-44. doi: 10.2337/db06-1464.
  • Winckler W, Weedon MN, Graham RR, et al. Evaluation of common variants in the six known maturity-onset diabetes of the young (MODY) genes for association with type 2 diabetes. Diabetes 2007;56:685-93.doi: 10.2337/db06-0202.
  • She L, Li W, Guo Y, et al. Association of glucokinase gene and glucokinase regulatory protein gene polymorphisms with gestational diabetes mellitus: A case-control study. Gene 2022; 824:146378. doi: 10.1016/j.gene.2022.146378.
  • Fujita H, Hara K, Shojima N, et al. Variations with modest effects have an important role in the genetic background of type 2 diabetes and diabetes-related traits. J Hum Genet 2012 Dec;57:776-9. doi: 10.1038/jhg.2012.110.
  • Leak TS, Langefeld CD, Keene KL, et al. Chromosome 7p linkage and association study for diabetes related traits and type 2 diabetes in an African American population enriched for nephropathy. BMC Med Genet 2010; 11:22. doi: 10.1186/1471-2350-11-22.

Year 2025, Volume: 38 Issue: 3, 242 - 251, 10.10.2025
https://doi.org/10.5472/marumj.1800187

Abstract

References

  • IDF Diabetes Atlas 2021, 10th edition https://diabetesatlas. org/atlas/tenth-edition/ (Accessed on January 17, 2022)
  • Ong KL, Stafford LK, McLaughlin SA, et al. (GBD 2021 Diabetes Collaborators) Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet 2023;402:203-34. doi:10.1016/S0140- 6736(23)01301-6.
  • American Diabetes Association. Standards of medical care in diabetes—2007. Diabetes Care 2007;30 Suppl 1: S4-S41. doi: 10.2337/dc07-S004. PMID: 17192377.
  • Henzen C. Monogenic diabetes mellitus due to defects in insulin secretion. Swiss Med Wkly 2012;142: w13690. doi: 10.4414/smw.2012.13690. PMID: 23037711.
  • Mughal SA, Thanabalasingham G, Owen KR. Biomarkers currently used for the diagnosis of maturity-onset diabetes of the young. Diabetes Management 2013;3: 71.doi:10.2217/dmt.12.82
  • Firdous P, Nissar K, Ali S, et al. Genetic testing of maturityonset diabetes of the young current status and future perspectives. Front Endocrinol (Lausanne) 2018; 9:253. doi:10.3389/fendo.2018.00253
  • Ansari N, Ramachandran V, Mohamad NA, et al. Associations of GCK (rs1799884), GCKR (rs780094), and G6PC2 (rs560887) gene polymorphisms with type 2 diabetes among Malay ethnics. Glob Med Genet 2023 ;10:12- 8. doi:10.1055/s-0042.176.0384
  • Li C, Yang Y, Liu X, Li Z, Liu H, Tan Q. Glucose metabolismrelated gene polymorphisms as the risk predictors of type 2 diabetes. Diabetol Metab Syndr 2020 ;12:97. doi: 10.1186/ s13098.020.00604-5.
  • Zhang X, Sun G, LI J, Han H, Chen, Q. Relationship between glucokinase gene 6 tag single nucleotide polymorphism sites and type 2 diabetes mellitus. Chin J Lab Med 2015;12: 827-32.
  • Yilmaz GS, Haliloglu B The role of glucokinase gen (GCK, MODY 2) variations in diabetes Panel-Abstracts.OP- 04 MEDICAL BIOCHEMISTRY 2018 ;1: 61.
  • Sun G, Zhang X, Li J, Han H, Chen Q. The relationship between glucokinase gene 4 tag single nucleotide polymorphism sites and type 2 diabetes mellitus Int J Lab Med 2016.; 12: 2507-10.
  • Bonnycastle LL, Willer CJ, Conneely KN, et al. Common variants in maturity-onset diabetes of the young genes contribute to risk of type 2 diabetes in Finns. Diabetes 2006;55:2534-40. doi: 10.2337/db06-0178
  • Frigeri HR, Auwerter NC, Koczicki L, et al. Polymorphisms rs144723656, rs2268574, and rs2268575 of the glucokinase gene are not associated with obese women with type 2 diabetes mellitus. Clin Biochem 2016 ;49:194-5. doi: 10.1016/j. clinbiochem. 2015.09.016.
  • Holmkvist J, Almgren P, Lyssenko V, et al. Common variants in maturity-onset diabetes of the young genes and future risk of type 2 diabetes. Diabetes 2008;57:1738-44. doi: 10.2337/db06-1464.
  • Winckler W, Weedon MN, Graham RR, et al. Evaluation of common variants in the six known maturity-onset diabetes of the young (MODY) genes for association with type 2 diabetes. Diabetes 2007;56:685-93.doi: 10.2337/db06-0202.
  • She L, Li W, Guo Y, et al. Association of glucokinase gene and glucokinase regulatory protein gene polymorphisms with gestational diabetes mellitus: A case-control study. Gene 2022; 824:146378. doi: 10.1016/j.gene.2022.146378.
  • Fujita H, Hara K, Shojima N, et al. Variations with modest effects have an important role in the genetic background of type 2 diabetes and diabetes-related traits. J Hum Genet 2012 Dec;57:776-9. doi: 10.1038/jhg.2012.110.
  • Leak TS, Langefeld CD, Keene KL, et al. Chromosome 7p linkage and association study for diabetes related traits and type 2 diabetes in an African American population enriched for nephropathy. BMC Med Genet 2010; 11:22. doi: 10.1186/1471-2350-11-22.
There are 18 citations in total.

Details

Primary Language English
Subjects Surgery (Other)
Journal Section Original Research
Authors

Yaşar Sertbaş 0000-0002-9685-4486

Seda Güleç 0000-0002-8119-2862

Fatma Tuba Akdeniz 0000-0002-6076-0509

Sadettin İlker Güvenç This is me 0000-0002-4394-2538

Özden Ezgi Üner 0000-0001-5158-5502

Meltem Sertbas 0000-0001-8987-7199

Hasan Aydın This is me 0000-0003-4246-0681

Turgay İsbir 0000-0002-7350-6032

Publication Date October 10, 2025
Submission Date June 17, 2025
Acceptance Date August 14, 2025
Published in Issue Year 2025 Volume: 38 Issue: 3

Cite

APA Sertbaş, Y., Güleç, S., Akdeniz, F. T., … Güvenç, S. İ. (2025). Potential association of GCK rs2268576 and rs741038 polymorphisms with type 2 diabetes mellitus in the Turkish population. Marmara Medical Journal, 38(3), 242-251. https://doi.org/10.5472/marumj.1800187
AMA Sertbaş Y, Güleç S, Akdeniz FT, et al. Potential association of GCK rs2268576 and rs741038 polymorphisms with type 2 diabetes mellitus in the Turkish population. Marmara Med J. October 2025;38(3):242-251. doi:10.5472/marumj.1800187
Chicago Sertbaş, Yaşar, Seda Güleç, Fatma Tuba Akdeniz, Sadettin İlker Güvenç, Özden Ezgi Üner, Meltem Sertbas, Hasan Aydın, and Turgay İsbir. “Potential Association of GCK Rs2268576 and Rs741038 Polymorphisms With Type 2 Diabetes Mellitus in the Turkish Population”. Marmara Medical Journal 38, no. 3 (October 2025): 242-51. https://doi.org/10.5472/marumj.1800187.
EndNote Sertbaş Y, Güleç S, Akdeniz FT, Güvenç Sİ, Üner ÖE, Sertbas M, Aydın H, İsbir T (October 1, 2025) Potential association of GCK rs2268576 and rs741038 polymorphisms with type 2 diabetes mellitus in the Turkish population. Marmara Medical Journal 38 3 242–251.
IEEE Y. Sertbaş, S. Güleç, F. T. Akdeniz, S. İ. Güvenç, Ö. E. Üner, M. Sertbas, H. Aydın, and T. İsbir, “Potential association of GCK rs2268576 and rs741038 polymorphisms with type 2 diabetes mellitus in the Turkish population”, Marmara Med J, vol. 38, no. 3, pp. 242–251, 2025, doi: 10.5472/marumj.1800187.
ISNAD Sertbaş, Yaşar et al. “Potential Association of GCK Rs2268576 and Rs741038 Polymorphisms With Type 2 Diabetes Mellitus in the Turkish Population”. Marmara Medical Journal 38/3 (October2025), 242-251. https://doi.org/10.5472/marumj.1800187.
JAMA Sertbaş Y, Güleç S, Akdeniz FT, Güvenç Sİ, Üner ÖE, Sertbas M, Aydın H, İsbir T. Potential association of GCK rs2268576 and rs741038 polymorphisms with type 2 diabetes mellitus in the Turkish population. Marmara Med J. 2025;38:242–251.
MLA Sertbaş, Yaşar et al. “Potential Association of GCK Rs2268576 and Rs741038 Polymorphisms With Type 2 Diabetes Mellitus in the Turkish Population”. Marmara Medical Journal, vol. 38, no. 3, 2025, pp. 242-51, doi:10.5472/marumj.1800187.
Vancouver Sertbaş Y, Güleç S, Akdeniz FT, Güvenç Sİ, Üner ÖE, Sertbas M, et al. Potential association of GCK rs2268576 and rs741038 polymorphisms with type 2 diabetes mellitus in the Turkish population. Marmara Med J. 2025;38(3):242-51.