Transcription Factor 7-Like-2 (TCF7L2) rs7903146 (C/T) Polymorphism in Patients with Type 2 Diabetes Mellitus

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Arig Aly Seif ◽  
Amira Ibrahim Hamed ◽  
Ahmed Mohamed Bahaaeldin ◽  
Walaa Ahmed Yousry Kabiel ◽  
Mohamed Ahmed Abo El Azm

Abstract Background Type 2 diabetes mellitus (T2DM) is a heterogeneous group of metabolic disorders characterized by the incapability of pancreatic beta cells to increase insulin secretion to compensate for insulin resistance in the peripheral tissues. T2DM is a multi-factorial disease including several environmental factors with the presence of genetic predisposition. The transcription factor 7-like-2 gene (TCF7L2) rs7903146 (C/T) polymorphism is one of the most susceptible genes to T2DM discovered to date, with contribution to the disease through the Wnt/β –catenin signaling pathway affecting pancreatic islet development, expression of several genes involved in insulin granules exocytosis and the incretin glucagon-like peptide 1 (GLP-1) gene. Aim of the Work In this study we aimed to investigate the potential association of the transcription factor 7-like-2 (TCF7L2) rs7903146 (C/T) gene polymorphism in patients with type 2 diabetes mellitus. Patients and Methods The study was a case- control study conducted on 70 T2DM patients recruited from the endocrinology clinic at Ain Shams University Hospitals, and 30 non diabetic healthy controls matched with the patients in age and sex. All subjects underwent full history taking, thorough clinical examination, routine laboratory investigations including haemoglobin A1c (HbA1c), lipid profile; total cholesterol (TC), triglycerides (TG), high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C) and determination of TCF7L2 gene polymorphism by real-time quantitative polymerase chain reaction (RT-PCR). Results The minor T allele of the rs7903146(C/T) SNP was associated with high risk of development of T2DM with an OR of 1.35 (95% CI: 0.68-2.6), the heterozygous genotype (CT) with an OR 1.16 (95% CI: 0.49-2.7) and the homozygous mutant genotype (TT) with OR of 3.16 (95% CI: 0.15-6.31), however, they were statistically insignificant (p-value >0.05). Conclusion Our study did not confirm the presence of significant association between the TCF7L2 rs7903146(C/T) polymorphism and T2DM, however, it pointed to the possibility of presence of high risk of development of T2DM in patients with TT genotype. Further studies with higher sample size are needed to clarify the association.

2020 ◽  
Vol 26 (3) ◽  
pp. 112-118
Author(s):  
Ahmed Mohamed Bahaaeldin ◽  
Arig Aly Seif ◽  
Amira Ibrahim Hamed ◽  
Walaa Ahmed Yousry Kabiel

<b><i>Introduction:</i></b> Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by the incapability of pancreas to increase insulin secretion to compensate for insulin resistance in the peripheral tissues. T2DM is a multifactorial disease including several environmental factors with the presence of genetic predisposition. The transcription factor 7-like-2 gene (<i>TCF7L2</i>) rs7903146 (C/T) polymorphism is one of the most susceptible genes to T2DM discovered to date, with contribution to the disease through the Wnt/β-catenin signaling pathway affecting pancreatic islet development, expression of several genes involved in insulin granules exocytosis, and the incretin glucagon-like peptide 1 (<i>GLP-1</i>) gene. Then, <i>TCF7L2</i> gene seems to affect diabetes susceptibility through B-cell dysfunction that is why we studied its association with T2DM in particular. <b><i>Objectives:</i></b> To investigate the potential association of the transcription factor 7-like-2 (<i>TCF7L2</i>) rs7903146 (C/T) gene polymorphism in patients with T2DM. <b><i>Methods:</i></b> A case-control study conducted on 70 T2DM patients recruited from the endocrinology clinic at Ain Shams University Hospitals, and 30 non-diabetic healthy controls age- and sex-matched with the patients. All subjects underwent full history taking; thorough clinical examination; routine laboratory investigations including hemoglobin A1c, total cholesterol, triglycerides, high-density lipoprotein-cholesterol, and low-density lipoprotein-cholesterol; and determination of <i>TCF7L2</i> gene polymorphism by qRT-PCR. <b><i>Results:</i></b> The minor T allele of the rs7903146(C/T) SNP was associated with high risk of development of T2DM with an OR of 1.35 (95% CI: 0.68–2.6) and the heterozygous genotype (CT) with an OR 1.16 (95% CI: 0.49–2.7); however, they were statistically insignificant (<i>p</i> value &#x3e;0.05). <b><i>Conclusion:</i></b> Our study did not confirm the presence of significant association between the <i>TCF7L2</i> rs7903146(C/T) polymorphism and T2DM; however, it pointed out the possibility of presence of high risk of development of T2DM in patients with TT genotype. Further studies with higher sample size are needed to clarify the association.


2011 ◽  
Vol 24 (4) ◽  
pp. 417-425 ◽  
Author(s):  
Luigi Brunetti ◽  
R. Keith Campbell

Purpose: The clinical experience and role in therapy of colesevelam in type 2 diabetes mellitus (T2DM) is discussed. Summary: Colesevelam HCl is a bile acid sequestrant (BAS) with proven efficacy in reducing elevated low-density lipoprotein cholesterol (LDL-C) in patients with primary hyperlipidemia. Colesevelam HCl gained food and drug administration (FDA) approval in 2008 as an adjunct to diet and exercise to improve glycemic control in adults with T2DM. In randomized controlled studies, colesevelam (add-on therapy with metformin, sulfonylureas, and insulin) has shown significant percentage reductions in glycosylated hemoglobin A1c (HbA1c) ranging from 0.5% to 0.54%. Reductions in LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C) ranging from –12.8% to –16.7% and –4.0% to –10.3%, respectively, were also observed. Although no direct comparisons have been made, the safety and tolerability profile of this agent appears to be better than other BAS, with the most common side effects being gastrointestinal related. Conclusion: Colesevelam is effective as an adjunct to diet and exercise to improve glycemic control in adults with T2DM. Due to its effects upon LDL-C and glycemic parameters and favorable safety profile, colesevelam can play a role in an array of T2DM patients.


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