Polymorphism in the transcription factor 7-like 2 (TCF7L2) gene is associated with impaired proinsulin conversion—A meta-analysis

Shen, Jingtao; Fang, Yun; Ge, Weihong

doi:10.1016/j.diabres.2015.04.020

Cited by 8 publications

(3 citation statements)

References 43 publications

(57 reference statements)

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“…Moreover, it has been confirmed that the impairment of insulin vesicle trafficking could be done by silencing TCF7L2 [29]. The T-allele of the TCF7L2 rs7903146 was an important risk factor for impaired proinsulin conversion, as has been found by a previous meta-analysis [30].…”

Section: Proinsulin Conversion and β-Cell Responsivitysupporting

confidence: 64%

Pivotal Role of Both TNF-α 238G/A and TCF7L2 C/T Gene Polymorphisms in Type 2 Diabetes

Hini

Ahmed

Hamed

et al. 2020

Open Access Maced J Med Sci

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Single nucleotide polymorphism (SNP) studies in the promoter region of tumor necrosis factor-alpha (TNF-α (238)) have suggested its role in increased insulin resistance and also in the progression from prediabetes to type 2 diabetes (T2DM). It has been reported that genetic variations in the promoter region regulate TNF-α production and transcription, and they influence susceptibility to inflammatory-related diseases. Impairment of normal functioning of the β-cells of pancreatic islets is one of the main causative factors for the suppression of insulin secretion. TNF-α is among the main stimuli that induce the inflammation in pancreatic islets which lead to the induction of apoptosis in β-cells of pancreatic islets. Transcription factor 7-like 2 (TCF7L2) gene has been found to be one of the most risky genes for prediabetes and progression toT2DM. However, the underlying mechanism of this is still unknown. This is a review article demonstrating the possible mechanisms of both TNF-α G/A 238 and TCF7L2 C/T gene polymorphisms in prediabetes and type 2 diabetes mellitus.

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Section: Proinsulin Conversion and β-Cell Responsivitysupporting

confidence: 64%

Pivotal Role of Both TNF-α 238G/A and TCF7L2 C/T Gene Polymorphisms in Type 2 Diabetes

Hini

Ahmed

Hamed

et al. 2020

Open Access Maced J Med Sci

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“…TCF7L2 is a transcription factor of which polymorphisms have been associated with cancers including colon and prostate [31]. However, this gene’s polymorphisms have been intensively studied in the context of diabetes-associated disorders [32].…”

Section: Introductionmentioning

confidence: 99%

Driver genes exome sequencing reveals distinct variants in African Americans with colorectal neoplasia

Ashktorab

Azimi

Varma³

et al. 2019

Oncotarget

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Background Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the United States. African Americans are disproportionately affected by CRC. Our hypothesis is that driver genes with known and novel mutations have an impact on CRC outcome in this population. Therefore, we investigated the variants’ profiles in a panel of 15 CRC genes. Patients & Methods Colorectal specimens (n=140) were analyzed by targeted exome sequencing using an Ion Torrent platform. Detected variants were validated in 36 samples by Illumina sequencing. The novel status of the validated variants was determined by comparison to publicly available databases. Annotated using ANNOVAR and in-silico functional analysis of these variants were performed to determine likely pathogenic variants. Results Overall, 121 known and novel variants were validated: APC (27%), AMER1 (3%) , ARID1 (7%), MSH3 (12%), MSH6 (10%), BRAF (4%), KRAS (6%), FBXW7 (4%), PIK3CA (6%), SMAD4 (5%), SOX9 (2%), TCF7L2 (2%), TGFBR2 (5%), TP53 (7%). From these validated variants, 12% were novel in 8 genes (AMER1, APC, ARID1A, BRAF, MSH6, PIK3CA, SMAD4, and TCF7L2 ). Of the validated variants, 23% were non-synonymous, 14% were stopgains, 24% were synonymous and 39% were intronic variants. Conclusion We here report the specifics of variants’ profiles of African Americans with colorectal lesions. Validated variants showed that Tumor Suppressor Genes (TSGs) APC and ARID1 and DNA Mismatch repair (MMR) genes MSH3 and MSH6 are the genes with the highest numbers of validated variants. Oncogenes KRAS and PIK3CA are also altered and likely participate in the increased proliferative potential of the mutated colonic epithelial cells in this population.

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“…Carriers of the risk alleles rs1225537 and rs7901346 in TCF7L2 have not only increased risk of T2DM, but also increased proinsulin and proinsulin-to-insulin ratio [34]. A metaanalysis revealed that the T-allele of the TCF7L2 rs7903146 is a significant risk factor for impaired proinsulin conversion [35]. Impaired proinsulin conversion may be one of the mechanisms of T2DM induction by TCF7L2.…”

Section: B-cell Apoptosis Proinsulin Conversion and B-cell Responsivitymentioning

confidence: 99%

Possible role of TCF7L2 in the pathogenesis of type 2 diabetes mellitus

Huang

Liao

Huang

et al. 2018

Biotechnology & Biotechnological Equipment

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With people's changing life style and dietary habits, the prevalence of type 2 diabetes mellitus (T2DM) has become much more serious than ever before. T2DM is a polygenic metabolic disorder, resulting from the interaction of genetic and various environmental factors. Among all the T2DM related genes, the transcription factor 7 like 2 (TCF7L2) gene is one of the most relevant risk-related genes for T2DM. However, the role of TCF7L2 in T2DM pathogenesis has not yet been interpreted thoroughly. Based on the experimental studies in recent years, this review discusses several possible mechanisms of T2DM pathogenesis induced by TCF7L2.

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Polymorphism in the transcription factor 7-like 2 (TCF7L2) gene is associated with impaired proinsulin conversion—A meta-analysis

Cited by 8 publications

References 43 publications

Pivotal Role of Both TNF-α 238G/A and TCF7L2 C/T Gene Polymorphisms in Type 2 Diabetes

Pivotal Role of Both TNF-α 238G/A and TCF7L2 C/T Gene Polymorphisms in Type 2 Diabetes

Driver genes exome sequencing reveals distinct variants in African Americans with colorectal neoplasia

Possible role of TCF7L2 in the pathogenesis of type 2 diabetes mellitus

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