Associations of transcription factor 7-Like 2 (TCF7L2) gene polymorphism in patients of type 2 diabetes mellitus from Khyber Pakhtunkhwa population of Pakistan

Hameed, Taha; Khan, Zahid; Imran, Muhammad; Ali, Shaukat; Albegali, Abdullah Abdo; Ullah, Muhammad Ikram; Ejaz, Hasan

doi:10.4314/ahs.v21i1.4

Cited by 12 publications

(4 citation statements)

References 35 publications

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“…They have reported a significant association of rs7903146 with T2DM in all the above populations [ 18 ]. A study on T2DM patients from the Khyber Pakhtunkhwa population showed a significant risk of T allele either in heterozygote or homozygous state [ 19 ]. Similar studies on African, Asian, and Brazilian subjects have reported a strong association of the SNP to T2DM [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic Association of Transcription Factor 7-Like-2 rs7903146 Polymorphism With Type 2 Diabetes Mellitus

Kumar,

Prakash,

Kumari

et al. 2024

Cureus

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Introduction: Type 2 diabetes mellitus (T2DM) mainly results from the inability of muscle, fat, and liver cells to uptake glucose due to insulin resistance or deficiency of insulin production by the pancreas. Predisposition to T2DM may be due to environmental, hereditary, or both factors. Although there are many genes involved in causing T2DM, transcription factor 7-like-2 gene (TCF7L2) rs7903146 (C/T) single nucleotide polymorphism (SNP) found in genome-wide association studies (GWAS) is susceptible to T2DM. TCF7L2 is involved in pancreatic beta cell proliferation and differentiation via the Wnt signaling mechanism. Objectives: To find the genetic association of TCF7L2 rs7903146 (C/T) gene polymorphism in patients with T2DM. Methods: A case-control study was conducted on 194 T2DM patients recruited from the endocrinology department at Indira Gandhi Institute of Medical Sciences, Patna, and 180 non-diabetic healthy controls that were age and sex-matched with the patients. All clinical examination and biochemical investigations like glycosylated hemoglobin (HbA1c), total cholesterol, triglycerides, high-density lipoprotein-cholesterol, and low-density lipoprotein-cholesterol; and determination of TCF7L2 gene polymorphism by allele-specific polymerase chain reaction (AS-PCR) were carried out for each subject. Results: The T allele of the rs7903146 (C/T) SNP was associated with a two-fold higher risk of T2DM and the heterozygous genotype (CT) with a 1.96 times higher risk. Conclusion: There is a high association of this SNP with the development of T2DM in the eastern Indian population. Serial monitoring of HbA1c should be done in an individual having this type of polymorphism for early detection of T2DM to prevent future complications.

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Section: Discussionmentioning

confidence: 99%

Genetic Association of Transcription Factor 7-Like-2 rs7903146 Polymorphism With Type 2 Diabetes Mellitus

Kumar,

Prakash,

Kumari

et al. 2024

Cureus

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“…Replication of case-control studies was carried out in different populations of women with GDM among the rs7903146 [ 25 , 26 , 27 , 28 , 29 , 30 ], rs2237892 [ 31 , 32 , 33 , 34 , 35 ], and rs5219 [ 35 , 36 , 37 , 38 ] SNPs. Meta-analysis studies have been carried out with rs7903146 [ 39 , 40 , 41 , 42 , 43 ], rs2237892 [ 42 , 44 ] and rs5219 SNPs [ 42 ] in women with GDM.…”

Section: Discussionmentioning

confidence: 99%

Saudi Community-Based Screening Study on Genetic Variants in β-Cell Dysfunction and Its Role in Women with Gestational Diabetes Mellitus

Alshammary

Al-Hakeem

Khan

2023

Genes

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Background: Diabetes (hyperglycemia) is defined as a multifactorial metabolic disorder in which insulin resistance and defects in pancreatic β-cell dysfunction are two major pathophysiologic abnormalities that underpin towards gestational diabetes mellitus (GDM). TCF7L2, KCNQ1, and KCNJ11 genes are connected to the mechanism of β-cell dysfunction. The purpose of this study was to investigate the genes associated with β-cell dysfunction and their genetic roles in the rs7903146, rs2237892, and rs5219 variants in Saudi women diagnosed with type 2 diabetes mellitus and GDM. Materials and Methods: In this case-control study, 100 women with GDM and 100 healthy volunteers (non-GDM) were recruited. Genotyping was performed using polymerase chain reaction (PCR), followed by restriction fragment length analysis. Validation was performed using Sanger sequencing. Statistical analyses were performed using multiple software packages. Results: Clinical studies showed a β-cell dysfunction positive association in women with GDM when compared to non-GDM women (p < 0.05). Both rs7903146 (CT vs. CC: OR-2.12 [95%CI: 1.13–3.96]; p = 0.01 & T vs. C: (OR-2.03 [95%CI: 1.32–3.11]; p = 0.001) and rs5219 SNPs (AG vs. AA: OR-3.37 [95%CI: 1.63–6.95]; p = 0.0006 & G vs. A: OR-3.03 [95%CI: 1.66–5.52]; p = 0.0001) showed a positive association with genotype and allele frequencies in women with GDM. ANOVA analysis confirmed that weight (p = 0.02), BMI (p = 0.01), and PPBG (p = 0.003) were associated with rs7903146 and BMI (p = 0.03) was associated with rs2237892 SNPs. Conclusions: This study confirms that the SNPs rs7903146 (TCF7L2) and rs5219 (KCNJ11) are strongly associated with GDM in the Saudi population. Future studies should address the limitations of this study.

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“…Various factors are responsible for developing Zn deficiency or can progress to alter the Zn metabolism in liver cirrhosis ( Table 1 ). These factors include insufficient intake alterations in amino acid and protein metabolism, lessened portosystemic shunts, hepatic extraction, impaired absorption due to alcohol influence, and the effects of endotoxins and cytokines, primarily IL-6 [ 63 , 64 ].…”

Section: Deficiency Of Zinc In Liver Diseasesmentioning

confidence: 99%

Biological Role of Zinc in Liver Cirrhosis: An Updated Review

et al. 2023

Self Cite

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Liver cirrhosis is a complication usually due to the consequence of persistent chronic liver disease. It is associated with different mechanisms, including hypoalbuminemia, impaired amino acid turnover, and micronutrient deficiencies. Consequently, cirrhotic patients can develop progressive complications like ascites, hepatic encephalopathy, and hepatocellular carcinoma. The liver is a vital organ that regulates the different metabolic pathways and transportation of trace elements. Zn is an indispensable micronutrient trace element involved in its crucial functions in cellular metabolic activity. Zn mediates its action by binding to a wide range of proteins; therefore, it imparts numerous biological effects, including cellular division, differentiation, and growth. It is also involved in critical processes for the biosynthesis of structural proteins and regulation of transcription factors and acts as a co-factor for the various enzymatic processes. As the liver is a significant regulator of Zn metabolism, its abnormalities lead to Zn deficiency, which has consequences on cellular, endocrine, immune, sensory, and skin dysfunctions. Conversely, Zn deficiency may modify the functions of hepatocytes and immune responses (acute phase protein production) in inflammatory liver diseases. This review has concisely stated the evolving indication of the critical role of Zn in biological processes and complications associated with liver cirrhosis pathogenesis due to Zn deficiency.

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Associations of transcription factor 7-Like 2 (TCF7L2) gene polymorphism in patients of type 2 diabetes mellitus from Khyber Pakhtunkhwa population of Pakistan

Cited by 12 publications

References 35 publications

Genetic Association of Transcription Factor 7-Like-2 rs7903146 Polymorphism With Type 2 Diabetes Mellitus

Genetic Association of Transcription Factor 7-Like-2 rs7903146 Polymorphism With Type 2 Diabetes Mellitus

Saudi Community-Based Screening Study on Genetic Variants in β-Cell Dysfunction and Its Role in Women with Gestational Diabetes Mellitus

Biological Role of Zinc in Liver Cirrhosis: An Updated Review

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