Association of TCF7L2 rs7903146 TT Genotype with Dyslipidemia in Type 2 Diabetes: A Case–Control Study in Pakistani Patients: Association of TCF7L2 rs7903146 TT Genotype with Dyslipidemia in Type 2 Diabetes

Shazia Azhar; Ghazala Masood Farrukh; Zurqa Khalid; Fareha Kashan Theba; Sikander Adil Mughal; Muhammad Khalid Siddiqui

doi:10.54393/pjhs.v7i5.3590

Authors

Shazia Azhar Department of Medical Technology, Baqai Institute of Medical Technology, Karachi, Pakistan
Ghazala Masood Farrukh Department of Physiology, Dow Medical College, Karachi, Pakistan
Zurqa Khalid Department of Physiology, Dow Medical College, Karachi, Pakistan
Fareha Kashan Theba Department of Physiology, Karachi Metropolitan University, Karachi, Pakistan
Sikander Adil Mughal Department of Physiology, Dow Medical College, Karachi, Pakistan
Muhammad Khalid Siddiqui Department of Physiology, Shaheed Mohtarma Benazir Bhutto Medical College, Karachi, Pakistan

DOI:

https://doi.org/10.54393/pjhs.v7i5.3590

Keywords:

Dyslipidemia, TCF7L2, Gene Polymorphism, Lipid Profile, Type 2 Diabetes

Abstract

Type 2 diabetes is often accompanied by dyslipidemia, which markedly increases cardiovascular risk. Genetic factors, particularly the TCF7L2 rs7903146 variant, have been implicated in alterations in glucose and lipid metabolism in T2DM. Objectives: To assess the association between dyslipidemia and the TCF7L2 rs7903146 polymorphism in patients with T2DM as compared to healthy controls. Methods: In Karachi, Pakistan, 100 T2DM patients and 100 age- and sex-matched healthy controls participated in case-control research. Blood samples obtained during fasting were examined for cholesterol and glucose levels. PCR-RFLP was used to genotype TCF7L2 rs7903146, and sequencing was used to confirm the results. Associations (p<0.050) were assessed using logistic regression and ANOVA. Results: TT genotype and T allele frequencies were greater in T2DM patients than in controls (p<0.010). Hence, genotype carriers had significantly higher triglycerides, total cholesterol, and LDL-C levels, and lower HDL-C levels. Multivariate logistic regression demonstrated that the TT genotype independently predicted dyslipidemia. Conclusions: The TCF7L2 rs7903146 TT genotype is strongly associated with dyslipidemia in T2DM patients and may assist in risk stratification and personalized management planning.

References

Liu J, Bai R, Chai Z, Cooper ME, Zimmet PZ, Zhang L. Low-and Middle-Income Countries Demonstrate Rapid Growth of Type 2 Diabetes: An Analysis Based on Global Burden of Disease 1990–2019 Data. Diabetologia. 2022 Aug; 65(8): 1339-52. doi: 10.1007/s00125-022-05713-6.

Zhao X, An X, Yang C, Sun W, Ji H, Lian F. The Crucial Role and Mechanism of Insulin Resistance in Metabolic Disease. Frontiers in Endocrinology. 2023 Mar; 14: 1149239. doi: 10.3389/fendo.2023.1149239.

Carmena R. Type 2 Diabetes, Dyslipidemia, And Vascular Risk: Rationale and Evidence for Correcting the Lipid Imbalance. American Heart Journal. 2005 Nov; 150(5): 859-70. doi: 10.1016/j.ahj.2005.04.027.

Hirano T. Clinical Significance of Small Dense Low‐Density Lipoprotein Cholesterol Measurement in Type 2 Diabetes. Journal of Diabetes Investigation. 2025 Mar; 16(3): 370-83. doi: 10.1111/jdi.14398.

Del Bosque-Plata L, Martínez-Martínez E, Espinoza-Camacho MÁ, Gragnoli C. The Role of TCF7L2 in Type 2 Diabetes. Diabetes. 2021 Jun; 70(6): 1220-8. doi: 10.2337/db20-0573.

Madhu SV, Mishra BK, Mannar V, Aslam M, Banerjee B, Agrawal V. TCF7L2 Gene Associated Postprandial Triglyceride Dysmetabolism-A Novel Mechanism for Diabetes Risk among Asian Indians. Frontiers in Endocrinology. 2022 Oct; 13: 973718. doi: 10.3389/fendo.2022.973718.

Jin T. Current Understanding on Role of the Wnt Signaling Pathway Effector TCF7L2 in Glucose Homeostasis. Endocrine Reviews. 2016 Jun; 37(3): 254-77. doi: 10.1210/er.2015-1146.

Saeed A, Virani SS, Mulukutla S, Chow CK. Dyslipidemia and Cardiovascular Disease Prevention in South Asians: A Review and Discussion of Causes, Challenges, and Management Strategies. Current Diabetes Reviews. 2021 Nov; 17(9): 74-86. doi: 10.2174/1573399817999210112192419.

Raza SA, Hassan M, Badar F, Rasheed F, Meerza F, Azam S et al. Cardiovascular Disease Risk Factors in Pakistani Population with Newly Diagnosed Type 2 Diabetes Mellitus: A Cross-Sectional Study of Selected Family Practitioner Clinics in Four Provinces of Pakistan (CardiP Study). The Journal of the Pakistan Medical Association. 2019; 69(3): 306.

Palizban A, Rezaei M, Khanahmad H, Fazilati M. Transcription Factor 7-Like 2 Polymorphism and Context-Specific Risk of Metabolic Syndrome, Type 2 Diabetes, and Dyslipidemia. Journal of Research in Medical Sciences. 2017 Jan; 22(1): 40. doi: 10.4103/1735-1995.202141.

Abbas SA, Raza ST, Mir SS, Siddiqi Z, Zaidi A, Zaidi Z et al. Association of Variants Rs7903146 and Rs290487 of TCF7L2 Gene with Diabetic Nephropathy and Co-Morbidities (Hypertension and Dyslipidemia) in Type 2 Diabetes Mellitus. Meta Gene. 2019 Jun; 20: 100561. doi: 10.1016/j.mgene.2019.100561.

Verma M, Loh NY, Sabaratnam R, Vasan SK, Van Dam AD, Todorčević M et al. TCF7L2 Plays a Complex Role in Human Adipose Progenitor Biology, Which Might Contribute to Genetic Susceptibility to Type 2 Diabetes. Metabolism. 2022 Aug; 133: 155240. doi: 10.1016/j.metabol.2022.155240.

Nguyen-Tu MS, Martinez-Sanchez A, Leclerc I, Rutter GA, Da Silva Xavier G. Adipocyte-Specific Deletion of Tcf7l2 Induces Dysregulated Lipid Metabolism and Impairs Glucose Tolerance in Mice. Diabetologia. 2021 Jan; 64(1): 129-41. doi: 10.1007/s00125-020-05292-4.

Jan A, Jan H, Ullah Z. Transcription Factor 7-Like 2 (TCF7L2): A Culprit Gene in Type 2 Diabetes Mellitus. Сахарный диабет. 2021; 24(4): 371-6. doi: 10.14341/DM12313.

Sen P, Alam SS, Jahan I, Saha P, Akter F, Shill LC. Association of the TCF7L2 rs7903146 Variant with Type 2 Diabetes Mellitus and Related Biomarkers: A Systematic Review. British Medical Journal Nutrition, Prevention and Health. 2025 Dec; 8(2). doi: 10.1136/bmjnph-2025-001205.

Chen N and Wang J. Wnt/β-Catenin Signaling and Obesity. Frontiers in Physiology. 2018 Jul; 9: 792. doi: 10.3389/fphys.2018.00792.

Hosseinpour-Niazi S, Mirmiran P, Hosseini S, Hadaegh F, Ainy E, Daneshpour MS et al. Effect of TCF7L2 on the Relationship Between Lifestyle Factors and Glycemic Parameters: A Systematic Review. Nutrition Journal. 2022 Sep; 21(1): 59. doi: 10.1186/s12937-022-00813-w.

Altall RM, Qusti SY, Filimban N, Alhozali AM, Alotaibi NA, Dallol A et al. SLC22A1 and ATM Genes Polymorphisms Are Associated with the Risk of Type 2 Diabetes Mellitus in Western Saudi Arabia: A Case-Control Study. The Application of Clinical Genetics. 2019 Nov: 213-9. doi: 10.2147/TACG.S229952.

Macedoni M, Hovnik T, Plesnik E, Kotnik P, Bratina N, Battelino T et al. Metabolic Control, ApoE Genotypes, and Dyslipidemia in Children, Adolescents and Young Adults with Type 1 Diabetes. Atherosclerosis. 2018 Jun; 273: 53-8. doi: 10.1016/j.atherosclerosis.2018.04.013.

Palmisano BT, Zhu L, Eckel RH, Stafford JM. Sex Differences in Lipid and Lipoprotein Metabolism. Molecular Metabolism. 2018 Sep; 15: 45-55. doi: 10.1016/j.molmet.2018.05.008.

Lamri A, De Paoli M, De Souza R, Werstuck G, Anand S, Pigeyre M. Insight into Genetic, Biological, and Environmental Determinants of Sexual-Dimorphism in Type 2 Diabetes and Glucose-Related Traits. Frontiers In Cardiovascular Medicine. 2022 Nov; 9: 964743. doi: 10.3389/fcvm.2022.964743.