Type 1 diabetes (T1D) is an autoimmune disease characterized by progressive destruction of pancreatic β-cells and chronic hyperglycemia. Genetic variants in ATP-sensitive potassium (K-ATP) channel genes, including ABCC8 and KCNJ11, may influence insulin secretion and susceptibility to diabetes. This study aimed to evaluate the association of ABCC8 rs1799854, ABCC8 rs1801261, and KCNJ11 rs5219 polymorphisms with T1D risk and related clinical and biochemical parameters in children. A case-control design was used, including 60 T1D patients and 60 age- and sex-matched healthy controls recruited between November 2024 and February 2025. Genomic DNA was extracted from peripheral blood, and genotyping was performed using PCR-RFLP for ABCC8 variants and ARMS-PCR for KCNJ11. Clinical and biochemical parameters, including BMI, lipid profile, HbA1c, and random blood glucose, were measured using standard automated methods. Statistical analysis included chi-square tests, t-tests, and ANOVA, with odds ratios (ORs) and 95% confidence intervals (CIs) used to estimate associations. The heterozygous CT genotypes of ABCC8 rs1799854 and KCNJ11 rs5219 were significantly associated with increased T1D risk (OR = 3.27, p = 0.003; OR = 6.10, p < 0.0001). In contrast, the ABCC8 rs1801261 TT genotype showed a protective association with T1D (OR = 0.22, p = 0.013). Significant genotype-related differences were observed in BMI, HDL cholesterol, HbA1c, and glucose levels. These findings suggest that ABCC8 and KCNJ11 polymorphisms may contribute to T1D susceptibility and metabolic variation in affected children. However, larger studies are required to confirm these associations.
Keywords
ABCC8 GeneKCNJ11 GeneT1DLipid Profile.
References
A. Zajec, K. Trebušak Podkrajšek, T. Tesovnik, R. Šket, B. Čugalj Kern, B. Jenko Bizjan, et al., “Pathogenesis of Type 1 Diabetes: Established Facts and New Insights,” Genes (Basel), vol. 13, no. 4, Apr. 2022, [Online]. Available: https://doi.org/10.3390/genes13040706.
M. Von Herrath, S. Sanda, and K. Herold, “Type 1 diabetes as a relapsing-remitting disease?,” Nature Reviews Immunology, vol. 7, no. 12, pp. 988-994, 2007.
R. A. Insel, J. L. Dunne, M. A. Atkinson, J. L. Chiang, D. Dabelea, P. A. Gottlieb, et al., “Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association,” Diabetes Care, vol. 38, no. 10, pp. 1964-1974, 2015, [Online]. Available: https://doi.org/10.2337/dc15-1419.
D. Dabelea, R. A. Bell, R. B. D’Agostino Jr, G. Imperatore, J. M. Johansen, B. Linder, et al., “Incidence of diabetes in youth in the United States,” JAMA, vol. 297, no. 24, pp. 2716-2724, 2007.
G. Stipancic, M. P. Sepec, L. L. Sabolic, A. Radica, V. Skrabic, S. Severinski, et al., “Clinical characteristics at presentation of type 1 diabetes mellitus in children younger than 15 years in Croatia,” J. Pediatr. Endocrinol. Metab., vol. 24, no. 9-10, pp. 665-670, 2011, [Online]. Available: https://doi.org/10.1515/jpem.2011.231.
E. F. Roche, A. M. McKenna, M. O’Regan, K. J. Ryder, H. M. Fitzgerald, and H. Hoey, “The incidence of type 1 diabetes in children under 15 years of age is rising again-a nationwide study,” Eur. J. Pediatr., vol. 182, no. 10, pp. 4615-4623, 2023, [Online]. Available: https://doi.org/10.1007/s00431-023-05125-.
M. J. Redondo, A. K. Steck, and A. Pugliese, “Genetics of type 1 diabetes,” Pediatr. Diabetes, vol. 19, no. 3, pp. 346-353, 2018.
M. Klak, M. Gomółka, P. Kowalska, J. Cichoń, F. Ambrożkiewicz, M. Serwańska-Świętek, et al., “Type 1 diabetes: genes associated with disease development,” Cent. Eur. J. Immunol., vol. 45, no. 4, pp. 439-453, 2020, [Online]. Available: https://doi.org/10.5114/ceji.2020.103386.
P. Haghvirdizadeh, Z. Mohamed, N. A. Abdullah, P. Haghvirdizadeh, M. S. Haerian, and B. S. Haerian, “KCNJ11: Genetic polymorphisms and risk of diabetes mellitus,” J. Diabetes Res., vol. 2015, p. 908152, 2015, [Online]. Available: https://doi.org/10.1155/2015/908152.
P. Haghverdizadeh, M. Sadat Haerian, P. Haghverdizadeh, and B. Sadat Haerian, “ABCC8 genetic variants and risk of diabetes mellitus,” Gene, vol. 545, no. 2, pp. 198-204, 2014, [Online]. Available: https://doi.org/10.1016/j.gene.2014.04.040.
F. M. Ashcroft, “ATP-sensitive potassium channelopathies: focus on insulin secretion,” J. Clin. Invest., vol. 115, no. 8, pp. 2047-2058, 2005, [Online]. Available: https://doi.org/10.1172/jci25495.
S. Reddy, S. Maddhuri, P. Nallari, V. Ananthapur, S. Kalyani, M. Krishna, et al., “Association of ABCC8 and KCNJ11 gene variants with type 1 diabetes in south Indians,” Egypt. J. Med. Hum. Genet., vol. 22, no. 1, p. 27, 2021, [Online]. Available: https://doi.org/10.1186/s43042-021-00149-w.
N. A. ElSayed, R. G. McCoy, G. Aleppo, K. Balapattabi, E. A. Beverly, K. Briggs Early, et al., “Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2025,” Diabetes Care, vol. 48, 2025.
M. Q. Waheeb, Y. A. Jabbar Alabdali, and H. A. Azez, “Gene Polymorphism Vitamin D receptor BsmI in Thalassemia Children in Al-Muthanna Province,” Indian J. Forensic Med. Toxicol., vol. 14, no. 3, 2020.
M. Q. Waheeb, H. A. Aziz, and Y. A. J. Alabdali, “Gene polymorphism vitamin D receptor FokI in thalassemia children in AL-Muthanna province,” Medico-Legal Update, vol. 19, no. 2, pp. 383-389, 2019.
D. Bodhini and V. Mohan, “Diabetes Burden in the IDF-MENA Region,” J. Diabetol., vol. 13, Suppl. 1, pp. S1-S2, 2022, [Online]. Available: https://doi.org/10.4103/jod.jod_125_22.
A. R. O. Jasim, N. A. Razzaq, A. T. A. Imeer, R. M. Rahem, A. A. H. Kadhum, and A. A. Al-Amiery, “Epidemiological profile and diabetes control of Type 1 Diabetes Mellitus patients in Karbala Governorate, Iraq,” F1000Research, vol. 12, p. 409, 2023.
D. Almahfoodh, M. Alabbood, A. Alali, and A. Mansour, “Epidemiology of type 1 diabetes mellitus in Basrah, Southern Iraq: A retrospective study,” Diabetes Res. Clin. Pract., vol. 133, pp. 104-108, 2017, [Online]. Available: https://doi.org/10.1016/j.diabres.2017.09.001.
D. M. Maahs, N. A. West, J. M. Lawrence, and E. J. Mayer-Davis, “Epidemiology of type 1 diabetes,” Endocrinol. Metab. Clin. North Am., vol. 39, no. 3, pp. 481-497, 2010, [Online]. Available: https://doi.org/10.1016/j.ecl.2010.05.011.
S. H. Zalzala, F. H. Al-Lami, and K. S. Fahad, “Epidemiological profile of type 1 diabetes among primary school children in Baghdad, Iraq,” J. Contemp. Med. Sci., vol. 6, no. 1, 2020.
I. Hormazábal-Aguayo, Y. Ezzatvar, N. Huerta-Uribe, R. Ramírez-Vélez, M. Izquierdo, and A. García-Hermoso, “Incidence of type 1 diabetes mellitus in children and adolescents under 20 years of age across 55 countries from 2000 to 2022: A systematic review with meta-analysis,” Diabetes/Metab. Res. Rev., vol. 40, no. 3, p. e3749, 2024.
L. A. Albishi, M. M. Altoonisi, S. M. Alblewi, R. H. Osman, N. A. Ahmed, and M. Fararjeh, “Clinical demographic patterns of type 1 diabetes in Saudi children in Tabuk City, 2000-2010,” J. Diabetes Mellitus, vol. 7, no. 2, p. 41, 2017.
A. A. Shaltout, D. Wake, T. A. Thanaraj, D. M. Omar, D. Al-AbdulRazzaq, A. Channanath, et al., “Incidence of type 1 diabetes has doubled in Kuwaiti children 0-14 years over the last 20 years,” Pediatr. Diabetes, vol. 18, no. 8, pp. 761-766, 2017.
M. Sidell, M. P. Martinez, T. Chow, and A. H. Xiang, “Types of diabetes during pregnancy and longitudinal BMI in offspring from birth to age 10 years,” Pediatr. Obes., vol. 16, no. 8, p. e12776, 2021.
N. L. Davis, J. D. Bursell, W. D. Evans, J. T. Warner, and J. W. Gregory, “Body composition in children with type 1 diabetes in the first year after diagnosis: relationship to glycaemic control and cardiovascular risk,” Arch. Dis. Child., vol. 97, no. 4, pp. 312-315, 2012.
M. Lestari, I. Faridah, R. Maliza, H. Dania, M. Widianingrum, and D. Perwitasari, “Identification of SNP rs1799854 ABCC8 gene and blood glucose levels in patients with type 2 diabetes mellitus at Moewardi hospital Surakarta Solo,” Pharmaciana, vol. 11, pp. 338-346, 2021, [Online]. Available: https://doi.org/10.12928/pharmaciana.v11i3.19100.
X. Zhou, C. Chen, D. Yin, F. Zhao, Z. Bao, Y. Zhao, et al., “A variation in the ABCC8 gene is associated with type 2 diabetes mellitus and repaglinide efficacy in Chinese type 2 diabetes mellitus patients,” Intern. Med., vol. 58, no. 16, pp. 2341-2347, 2019.
F. M. Ashcroft, “KATP Channels and the Metabolic Regulation of Insulin Secretion in Health and Disease: The 2022 Banting Medal for Scientific Achievement Award Lecture,” Diabetes, vol. 72, no. 6, pp. 693-702, 2023, [Online]. Available: https://doi.org/10.2337/dbi22-0030.
S. M. Raj, J. M. M. Howson, N. M. Walker, J. D. Cooper, D. J. Smyth, S. F. Field, et al., “No association of multiple type 2 diabetes loci with type 1 diabetes,” Diabetologia, vol. 52, no. 10, pp. 2109-2116, 200.